Chapter 19

Viruses

KEY CONCEPTS

19.1 Avirus consists of a nucleic acid surroundedby a protein coat

19.2 Viruses reproduce only in host cells19.3 Viruses, viroids, and prions are formidable

pathogens in animals and plants

The photo in Figure 19.1 shows a remarkable event:

the attack of a bacterial cell by numerous structuresthat resemble miniature lollipops. These structures,

a type of virus called T4 bacteriophage, are seen infectingthe bacterium Escherichia coli in this colorized SEM. Byinjecting its DNA into the cell, the virus sets in motion agenetic takeover of the bacterium, recruiting cellular machinery to mass-produce many new viruses.

Recall that bacteria and other prokaryotes are cells muchsmaller and more simply organized than those of eukaryotes,such as plants and animals. Viruses are smaller and simpler still.Lacking the structures and metabolic machinery found in cells,

most viruses are little more than genes packaged in protein coats.Are viruses living or nonliving? Early on, they were consid

ered biological chemicals; in fact, the Latin root for the wordvirus means "poison:' Because viruses are capable of causing a

wide variety of diseases and can be spread between organisms,researchers in the late 1800s saw a parallel with bacteria andproposed that viruses were the simplest of living forms. However, viruses cannot reproduce or carry oul metabolic activitiesoutside of a host cell. Most biologists studying viruses todaywould probably agree that they are not alive but exist in a shadyarea betv.'een life-forms and chemicals. The simple phrase usedrecently by two researchers describes them aptly enough:Viruses lead ~a kind of borrowed life."

... Figure 19.1 Are the tiny viruses infecting this E. colicell alive?

To a large extent, molecular biology was born in the laboratories of biologists studying viruses that infect bacteria. Experiments with viruses provided important evidence thatgenes are made ofnucleic acids, and they were critical in work·ing out the molecular mechanisms of the fundamental

processes of DNA replication, transcription, and translation.Beyond their value as experimental systems, viruses have

unique genetic mechanisms that are interesting in their ownright and that also help us understand how viruses cause disease. In addition, the study of viruses has led to the development of techniques that enable scientists to manipulate genesand transfer them from one organism to another. These techniques play an important role in basic research, biotechnology,and medical applications. For instance, viruses are used asagents of gene transfer in gene therapy (see Chapter 20).

In this chapter, we will explore the biology of viruses. Wewill begin with the structure of these simplest of all geneticsystems and then describe their reproductive cycles. Next, we

will discuss the role of viruses as disease-causing agents, orpathogens, and conclude by considering some even simplerinfectious agents, viroids and prions.

rZI~"i::::::i~s of a nucleic acidsurrounded by a protein coat

Scientists were able to detect viruses indirectly long beforethey were actually able to see them. The story of how viruseswere discovered begins near the end of the 19th century.

The Discovery of Viruses: Scientific tnquiry

Tobacco mosaic disease stunts the growth of tobacco plantsand gives their leaves a mottled, or mosaic, coloration. In1883, AdolfMayer, a German scientist, discovered that he could

381

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What causes tobacco mosaic disease?

)e Rubbed filtered

sap on healthytobacco plants

6 Passed sapthrough aporcelam filterknown to trapbacteria

\

SOURCE

RESULTS

GExtracted sapfrom tobaccoplant withtobacco mosaicdisease

When the filtered sap was rubbed on healthyplants. they became infected. Their sap. when extraded and filtered, could then ad as the source of infection for another groupof plants. Each successive group of plants developed the diseaseto the same extent as earlier groups,

CONCLUSiON The infectious agent was apparently not a bacterium because it could pass through a bacterium-trapping filter.The pathogen must have been reproducing in the plants becauseIts ability to cause disease was undiluted after several transfersfrom plant to plant.

EXPERIMENT In the late 18005. Martmus 8eijerinck. of theTechnical School in Delft, the Netherlands. investigated the properties of the agent that causes tobacco mosaic disease (thencalled spot disease).

• FI 19.2

M J ~JerirKk, Concerning a contagium vivum fluidumas CilUse of the spol disease of toiMcco leaves, VerhiJndelingen der Koninl:)ieakademie WetrenxlliJppen te Amsterdam 653-21 (1898) Translationpubtished in English ilS Phytopathological CIi!SSicl Number 7 (1942), AmericanPhytopathologICal >ociety Press, 51. PilUl, MN.

o Healthy plants becameinfected

viruses consist of multiple molecules of nucleic acid, The

smallest viruses known have only four genes in their genome,while the largest have several hundred to a thousand. Forcomparison, bacterial genomes contain about 200 to a fewthousand genes.

_lm,nIM If Beijerinck had observed that the infection of eachgroup was weaker than that of the previous group and that ultimately the sap could no longer cause disease, what might hehave concluded?

The tiniest viruses are only 20 nm in diameter-smaller thana ribosome. Millions could easily fit on a pinhead. Even thelargest known virus, which has a diameter of several hundrednanometers, is barely visible in the light microscope. Stanley'sdiscovery that some viruses could be crystallized was exciting

and puzzling news. Not even the simplest of cells can aggregate into regular crystals. But ifviruses are not cells, then whatare they? Examining the structure of viruses more closely reveals that they are infectious particles consisting of nucleicacid enclosed in a protein coat and, in some cases, a membra

nous envelope.

Viral Cenomes

We usually think of genes as being made of double-strandedDNA-the conventional double helix-but many viruses defy

this convention. Their genomes may consist of doublestranded DNA, single-stranded DNA, double-stranded RNA,

or single-stranded RNA, depending on the kind of virus. Avirus is called a DNA virus or an RNA virus, according to thekind of nucleic acid that makes up its genome. In either case,the genome is usually organized as a single linear or circularmolecule of nucleic acid, although the genomes of some

transmit the disease from plant to plant by rubbing sap extracted from diseased leaves onto healthy plants. After an unsuccessful search for an infectious microbe in the sap, Mayersuggested that the disease was caused by unusually small bac

teria that were invisible under a microscope. This hypothesiswas tested a decade later by Dimitri lvanowsky, a Russian bi

ologist who passed sap from infected tobacco leaves througha filter designed to remove bacteria. After filtration, the sapstill produced mosaic disease.

But Ivanowsky clung to the hypothesis that bacteria causedtobacco mosaic disease. Perhaps, he reasoned, the bacteria

were small enough to pass through the filter or made a toxinthat could do so. The second possibility was ruled out whenthe Dutch botanist Martinus Beijerinck carried out a classicseries of experiments that showed that the infectious agent inthe filtered sap could reproduce (Figure 19.2).

In fact, the pathogen reproduced only within the host it in

fected. in further experiments, Beijerinck showed that unlikebacteria used in the lab at that time, the mysterious agent ofmosaic disease could not be cultivated on nutrient media in

test tubes or petri dishes. Beijerinck imagined a reproducingparticle much smaller and simpler than a bacterium, and he isgenerally credited with being the first scientist to voice theconcept of a virus. His suspicions were confirmed in 1935

when the American scientist Wendell Stanley crystallized theinfectious particle, now known as tobacco mosaic virus(TMV). Subsequently, TMV and many other viruses were actually seen with the help of the electron microscope.

Siruciure of Viruses

382 UNIT THREE Genetics

Capsids and Envelopes

The protein shell enclosing the viral genome is called a capsid.Depending on the type of virus, the capsid may be rod-shaped,polyhedral, or more complex in shape (like T4). Capsids arebuilt from a large number ofprotein subunits calledcapsomeres,but the number of different kinds of proteins in a capsid is usually small. Tobacco mosaic virus has a rigid, rod-shaped capsidmade from over a thousand molecules ofa single type ofproteinarranged in a helix; rod~shaped viruses are commonly calledhelical viruses for this reason (Figure 19.3a). Adenoviruses,which infect the respiratory tracts of animals, have 252 identical protein molecules arranged in a polyhedral capsid with 20triangular facets-an icosahedron; thus, these and other similarly shaped viruses are referred to as icosahedral viruses(Figure 19.3b).

Some viruses have accessory structures that help them infecttheir hosts. For instance, a membranous envelope surroundsthe capsids ofinfluenza viruses and many other viruses found in

animals (Figure 19.3c). These viral envelopes, which are derived from the membranes of the host cell, contain host cellphospholipids and membrane proteins. They also contain proteins and glycoproteins of viral origin. (Glycoproteins are proteins with carbohydrates covalently attached.) Some virusescarry a few viral enzyme molecules within their capsids.

Many of the most complex capsids are found among theviruses that infect bacteria, called bacteriophages, or simply phages. The first phages studied included seven that infect E. coli. These seven phages were named type 1 (Tl),type 2 (T2), and so forth, in the order of their discovery. Thethree T-even phages (T2, T4, and T6) turned out to be verysimilar in structure. Their capsids have elongated icosahedral heads enclosing their DNA. Attached to the head is aprotein tail piece with fibers by which the phages attach to abacterium (Figure 19.3d). In the next section, we'll examinehow these few viral parts function together with cellularcomponents to produce large numbers of viral progeny.

80-200 nm (diameter)

RNA

Capsomereof capsid

18 x 250 nm

Glycoprotein

70-90 nm (diameter)

Membranousenvelope

RNADNA

80x225nm

~

20 nm(a) Tobacco mosaic virus has a

helICal capsid with the overallshape of a rigid rod.

50 nm(b) Adenoviruses have an

icosahedral capsid with aglycoprotein spike at eachvertex.

50 nm(c) Influenza viruses have an

outer envelope studded withglycoprotein spikes. Thegenome consists of eightdifferent RNA molecules, eachwrapped in a helical capsid.

f-----<50 nm

(d) Bacteriophage T4, like other"T-even" phages, has acomplex capsid consisting ofan icosahedral head and a tailapparatus.

... Figure 19.3 Viral structure. Viruses aremade up of nucleic acid (DNA or RNA) enclosedin a protein coat (the capsid) and sometimesfurther wrapped in a membranous envelope.

The individual protein subunits making up thecapsid are called capsomeres. Although diversein size and shape, viruses have commonstructural features, most of which appear in the

four examples shown here. (All the micrographsare colorized TEMs.)

(Il"'PTE~ NINHHN Viruses 383

o Viral genomesand capsid proteinsself-assemble intonew virus particles.which exit the cell.

o Meanwhile, hostenzymes transcribe theviral genome into viralmRNA, which hostribosomes use to makemore capsid proteins.

"•••Capsid •••••• •proteins ••••••••:

••••••••; .•••

~....

• • ••• ••·,U·:·~r

\

••••,...• ••••••Vi,,/ ~\NW-J",Viral DNA ~

~

Capsid

making viral nucleic acids, as well as enzymes, ribosomes,tRNAs, amino acids, ATP, and other components needed formaking the viral proteins. Most DNA viruses use the DNApolymerases of the host cell to synthesize new genomes along

the templates provided by the viral DNA. In contrast, to repli

cate their genomes, RNA viruses use vi rally encoded poly·merases that can use RNA as a template. (Uninfected cellsgenerally make no enzymes for carrying out this process.)

After the viral nucleic acid molecules and capsomeres areproduced, they spontaneously self-assemble into new viruses.In fact, researchers can separate the RNA and capsomeres ofTMVand then reassemble complete viruses simply by mixingthe components together under the right conditions. The simplest type of viral reproductive cycle ends with the exit of

fJ Host enzymesreplicate the viralgenome.

o Virus enters celland is uncoated,releasing viral DNA VIRUSand capsid proteins.

.. Figure 19.4 Asimplified viral reproductive cycle. A virus isan obligate intracellular parasite that uses the eqUipment and smallmolecules of its host cell to reproduce. In this simplest of viral cycles, theP<lrasite is aDNA virus with a capsid consisting of a single type of protein.

D Label each of the straight black arrows with one wordrepresenting the name of the process that is occurring.

19.1CONCEPT CHECI(

Viruses lack metabolic enzymes and equipment for makingproteins, such as ribosomes. They are obligate intracellularparasites; in other words, they can reproduce only within ahost celL It is fair to say that viruses in isolation are merelypackaged sets of genes in transit from one host cell to another.

Each type of virus can infect cells of only a limited varietyof hosts, called the host range of the virus. This host specificity results from the evolution of recognition systems by thevirus. Viruses identify host cells by a "lock-and-key" fit between viral surface proteins and specific receptor moleculeson the outside of cells. (According to one model, such receptor molecules originally carried out functions that benefited

the host cell but were co-opted later by viruses as portals ofen·try.) Some viruses have broad host ranges. For example, WestNile virus and equine encephalitis virus are distinctly differentviruses that can each infect mosquitoes, birds, horses, and hu

mans. Other viruses have host ranges so narrow that they infect only a single species. Measles virus, for instance, caninfect only humans. Furthermore, viral infection of multicellular eukaryotes is usually limited to particular tissues. Humancold viruses infect only the cells lining the upper respiratorytract, and the AIDS virus binds to receptors present only oncertain types of white blood cells.

General Features of Viral Reproductive Cycles

1. Compare the structures of tobacco mosaic virus(TMV) and influenza virus (see Figure 19.3).

2. _i*,.o14 In 2005, scientists discovered a virus

that could, under certain conditions, develop pointedprojections at each end while outside a host cell. How

does this observation fit with the characterization ofviruses as nonliving?

For suggested answers, see Appendix A.

A viral infection begins when a virus binds to a host cell andthe viral genome makes its way inside (Figure 19.4). Themechanism of genome entry depends on the type of virus andthe type of host cell. For example, T·even phages use theirelaborate tail apparatus to inject DNA into a bacterium (seeFigure 19.3d). Other viruses are taken up by endocytosis or, in

the case of enveloped viruses, by fusion of the viral envelopewith the plasma membrane. Once the viral genome is inside,the proteins it encodes can commandeer the host, reprogramming the cell to copy the viral nucleic acid and manufacture viral proteins. The host provides the nucleotides for


hundreds or thousands of viruses from the infected host cell,a process that often damages or destroys the cell. Such cellulardamage and death, as well as the body's responses to this destruction, cause many of the symptoms associated with viralinfections. The viral progeny that exit a cell have the potentialto infect additional cells, spreading the viral infection.

There are many variations on the simplified viral reproductive cycle we have traced in this general description. We willnow take a closer look at some of these variations in bacterialviruses (phages) and animal viruses; later in the chapter, wewill consider plant viruses.

Reproductive Cycles of Phages

Phages are the best understood of all viruses, although someof them are also among the most complex. Research onphages led to the discovery that some double-stranded DNAviruses can reproduce by two alternative mechanisms: thelytic cycle and the lysogenic cycle.

The Lytic Cycle

A phage reproductive cycle that culminates in death of thehost cell is known as a lytic cycle. The term refers to the last

stage of infection, during which the bacterium lyses (breaksopen) and releases the phages that were produced within thecell. Each of these phages can then infect a healthy cell, and afew successive lytic cycles can destroy an entire bacterial population in just a few hours. Aphage that reproduces only by alytic cycle is a virulent phage. Figure 19.5 illustrates the major steps in the lytic cycle ofT4, a typical virulent phage. Thefigure and legend describe the process, which you shouldstudy before proceeding.

After reading about the lytic cycle, you may wonder whyphages haven't exterminated all bacteria. In fact, phage treatments have been used medically in some countries to help control bacterial infections in patients. Solutions containingbacteriophages have also been sprayed on chicken carcasses,significantly reducing bacterial contamination ofpoultryon theway to the marketplace. Bacteria are not defenseless, however.First, natural selection favors bacterial mutants ""1th receptorsthat are no longer recognized by a particular type ofphage. Second, when phage DNA successfully enters a bacterium, theDNA often is identified as foreign and cut up by cellular enzymes called restriction enzymes, which are so named because their activity restricts the ability of the phage to infectthe bacterium. The bacterial cell's own DNA is methylated in a

/

o Attachment. The T4 phage usesits tail fibers to bind to specificreceptor sites on the outer surfaceof an E. coli cell. A

U Entry of phage DNAand degradation of hostDNA. The sheath of thetail contracts, injecting thephage DNA mto the celland leaving an empty

~ capsid outside. The cell'se:::::.---J DNA is hydrolyzed.

'\

o Release. The phagedirects production of anenzyme that damages thebacterial cell wall, allowingfluid to enter. The cellswells and finally bursts,releasing 100 to 200phage particles.

I I "- -I I I o Assembly. Three separate sets of proteins e Synthesis of viral genomes and

self·assemble to form phage heads, tails, proteins. The phage DNA directs

~and tail fibers The phage genome is production of phage proteins and

Ipackaged inside the capsid as the head copies of the phage genome by hostforms. enzymes, using components within. the cell.Head Tail Tail fibers

.. Figure 19.5 The lytic cycle ofphage T4, a virulent phage. PhageT4 has almost 300 genes. which aretranscribed and translated using the hostceli's machinery. One of the first phagegenes translated alter the viral DNAenter; the host cell codes for an enzymethat degrades the host cell's DNA (step 2);the phage DNA is protected frombreakdown because it contains amodified form of cytosine that is notrecognized by the enzyme. The entirelytic cycle. from the phage's first contactwith the cell surface to cell lysis, takesonly 20-30 minutes at 3rc.

Phage assembly

(IlAPTE~ NINHHN Viruses 385

way that preventsattack by its own restriction enzymes. But justas natural selection favors bacteria with mutant receptors or effective restriction enzymes, it also favors phage mutants thatcan bind the altered re<eptors or are resistant to particular restriction enzymes. Thus, the parasite-host relationship is in

constant evolutionary flux.There is yet a third important reason bacteria have been

spared from extinction as a result of phage activity. Instead oflysing their host cells, many phages coexist with them in a statecalled lysogeny, which we'll now discuss.

The Lysogenic Cycle

In contrast to the lytic cycle, which kills the host cell, thelysogenic cycle allows replication of the phage genome without destroying the host. Phages capable of using both modesof reproducing within a bacterium are called temperatephages. A temperate phage called lambda, written with theGreek letter f.., is widely used in biological research. Phage f..resembles T4, but its tail has only one, short tail fiber.

Infection of an £ coli cell by phage Abegins when the phagebinds to the surface ofthe cell and injects its linear DNA genome(Figure 19.6). Within the host, the ADNA molecule forms a circle. \'({hat happens next depends on the reproductive mode: lyticcycle or lysogenic cycle. During a lytic cycle, the viral genes im-

mediately tum the host cell into a !I.-producing factory, and thecell soon lyses and releases its viral products. During a lysogeniccycle, however, the !I. DNA molecule is incorporated into a specific site on the E. ro/i chromosome by viral proteins that breakboth circular DNA molecules and join them to each other. \Vhenintegrated into the bacterial chromosome in this way, the viralDNA is known as a prophage. One prophage gene codes for aprotein that prevents transcription of most of the otherprophage genes. Thus, the phage genome is mostly silent withintile bacterium. Every time the E. coli cell prepares to divide, itreplicates tile phage DNA along with its own and passes thecopies on to daughter cells. Asingle infected cell can quickly giverise to a large population of bacteria carrying the virus inprophage form. This mechanism enables viruses to propagatewithout killing the host cells on which they depend.

The term lysogenic implies that prophages are capable ofgenerating active phages that lyse their host cells. This occurswhen the !I. genome is induced to exit the bacterial chromosome and initiate a lytic cycle. An environmental signal, suchas a certain chemical or high-energy radiation, usually triggersthe switchover from the lysogenic to the lytic mode.

In addition to the gene for the transcription-preventingprotein, a few other prophage genes may be expressed during lysogeny. Expression of these genes may alter the host'sphenotype, a phenomenon that can have important medical

Many cell divisionsproduce a largepopulatiorl ofbacteria infectedwith the prophage.

I

The bacterium reproduces normally.copying the prophage andtransmitting it to daughter cells,

/Phage DNA integrates intothe bacterial chromosome.becomirlg a prophage,

ILysogenk cycle I

Daughter cellwith prophage

0'

Occasionally, a prophage \exits the bacterial chromosome,

'~~!:==:::!!=o.i' ...itiating a lytic cycle.

---,---,-----;-, (e90Lytic (yde I

Certain factorsdetermine whether

The phage attaches to ahost cell and injects its DNA.

New phage DNA andproteins are synthesized andassembled into phages.

The cell lyses, releasing phages,

""

Phage

... Figure 19.6 The lytic and lysogeniccycles of phage A, a temperate phage.After entering the bdcterial cell arld cirrularizirlg,the,,- DNA can immediately initiate the proouetion

of a large number of progeny phages (lytic cycle)or integrate into the bacterial chromosome(lysogenic cycle), In most cases, phage "- followsthe lytic pathway, which is similar to that detailed

in Figure 19.5. However, once a lysogenic cyclebegins, the prophage may be carried in the hostcell's chromosome for many generations, Phage "has one main tail fiber, which is short.


IV. Single-stranded RNA (ssRNA); serves as mRNA

II. Single-stranded DNA (ssDNA)

Parvovirus No B19 parvovirus (mild rash)

Reproductive Cycles of Animal Viruses

Viral Envelopes

An animal virus equipped with an envelope-that is, an outermembrane-uses it to enter the host cell. Protruding from theouter surface of this envelope are viral glycoproteins that bindto specific receptor molecules on the surface of a host cell.figure 19.7, on the next page, outlines the events in the reproductive cycle of an enveloped virus with an RNA genome.The protein parts ofenvelope glycoproteins are made by ribosomes bound to the endoplasmic reticulum (ER) of the hostcell; cellular enzymes in the ER and Golgi apparatus then addthe sugars. The resulting viral glycoproteins, embedded in hostcell-derived membrane, are transported to the cell surface. Ina process much like exocytosis, new viral capsids are wrappedin membrane as they bud from the cell. In other words, the viral envelope is derived from the host cell's plasma membrane,although some of the molecules of this membrane are specified by viral genes. The enveloped viruses are now free to infect other cells. This reproductive cycle does not necessarilykill the host cell, in contrast to the lytic cycles of phages.

Some viruses have envelopes that are not derived from plasmamembrane. Herpesviruses, for example, are temporarily cloakedin membrane derived from the nuclear envelopeofthe host; theythen shed this membrane in the cytoplasm and acquire a new envelope made from membrane of the Golgi apparatus. These

Everyone has suffered from viral infections, whether cold sores,influenza, or the common cold. Like all viruses, those that causeillness in humans and other animals can reproduce only insidehost cells. Manyvariationson the basic scheme ofviral infectionand reproduction are represented among the animal viruses.One key variable is the nature of the viral genome: Is it composed of DNA or RNA? Is it double-stranded or singlestranded? The nature ofthe genome is the basis for the commonclassification of viruses shown in 1able 19.1. Single-strandedRNA viruses are further classified into three classes (lV-VI) according to how the RNA genome functions in a host cell.

Whereas few bacteriophages have an envelope or RNAgenome, many animal viruses have both. In fact, nearly all an·imal viruses with RNA genomes have an envelope, as do somewith DNA genomes (see Table 19.1). Rather than consider allthe mechanisms of viral infection and reproduction, we willfocus on the roles of viral envelopes and on the functioning ofRNA as the genetic material of many animal viruses.

significance. Forexample, the three species ofbacteria that causethe human diseases diphtheria, botulism, and scarlet fever wouldnot be so harmful to humans without certain prophage genesthat cause the host bacteria to make toxins. And the differencebetween the E. coli strain that resides in our intestines and the0157:H7 strain that has caused several deaths by food poisoningappears to be the presence ofprophages in the 0157:H7 strain.

Measles virus; mumps virus

Rabies virus

Rhinovirus (common cold);poliovirus, hepatitis Avirus,and other enteric (intestinal)viruses

Severe acute respiratory syndrome (SARS)

Yellow fever virus; West Nilevirus; hepatitis Cvirus

Rubella virus; equineencephalitis viruses

Papillomavirus (warts, cervicalcancer); polyomavirus(tumors)

Herpes simplex I and II (coldsores, genital sores); varicellazoster (shingles, chickenpox); Epstein-Barr virus(mononucleosis, Burkitt'slymphoma)

Smallpox virus;cowpox virus

y~

y~

Envelope Examples/Disease

No

Classes of Animal Viruses

Poxvirus

Picornavirus

Coronavirus

V. ssRNA; template for mRNA synthesis

Filovirus Yes Ebola virus(hemorrhagic fever)

Influenza virus

Flavivirus

Adenovirus No(see Figure 19.3b)

Papovavirus No

Herpesvirus y~

VI. ssRNA; template for DNA synthesis

Retrovirus Yes K1V, human(see Figure 19.8) illlmunodeficiencyvirus

(AIDS); RNA tumor viruses(leukemia)

Paramyxovirus

Rhabdovirus

Togavirus

III. Double·stranded RNA (dSRNA)

Reovirus No Rotavirus (diarrhea);Colorado tick fever virus

Orthomyxovirus(see Figures 19.3cand 19.9b)

I. Double·stranded DNA (dSDNA)

Respiratory diseases; tumors

1"'1'.1

ClasslFamily


o Each new virus budsfrom the cell, its envelope studded with viralglycoproteins embeddedin membrane derivedfrom the host cell.

e The viral genome (red)functions as a template forsynthesis of complementaryRNA strands (pink) by a viralenzyme.

() New copies of viralgenome RNA are madeusing complementary RNAstrands as templates.

e The c03psid and viral genomeenter the cell. Digestion of thecapsid by cellular enzymes releasesthe viral genome.

-

HOST CEll

\N'V'V\IV\ Viral genome (RNA)

Template ~

o Glycoproteins on the viral envelope~:;~{.__~ bind to specific receptor molecules (not

shown) on the host cell, promotingviral entry into the cell.

Capsid

RNA----lir

mRNA~ j/

ER II '\ /C",;d...... ••(/ proteins" Glyco- .0••••0

... proteins • 0. °: ..1 ••"~"" -... ..~

"Vesicles transport L_~I,;~----::fenvelope glycoproteins to '-

the plasma membrane.

o A capsid assemblesaround each viral

genome molecule.

Envelope (withglycoproteins)

o Complementary RNAstrands also function as mRNA,

which is translated into bothcapsid proteins (in the cytosol)and glycoproteins for the viral

envelope (in the ER andGolgi apparatus).

.... Figure 19.7 The reproductive cycleof an enveloped ANA virus. Shown here isa virus with a single-stranded RNA genome thatfunctions as a template for synthesis of mRNA.Some enveloped viruses enter the host cell by

fusion of the envelope with the ceil's plasmamembrane; others enter by endocytosis, For allenveloped RNA viruses. the formation of newenvelopes for progeny viruses occurs by themechanism depicted in this figure,

1:'1 Name a virus thar has infected you and.. has a reproductive cycle marching thisone, (Hint: See Table 19.1.)

viruses have a double-stranded DNA genome and reproducewithin the host cell nucleus, using a combination of viral andcellular enzymes to replicate and transcribe their DNA. In thecase of herpesviruses, copies of the viral DNA can remain behind as mini-chromosomes in the nuclei of certain nerve cells.There they remain latent until some sort of physical or emotional stress triggers a new round of active virus production.The infection of other cells by these new viruses causes the blisters characteristic of herpes, such as cold sores or genital sores.Once someone acquires a herpesvirus infection, flare-ups mayrecur throughout the person's life.

RNA as Viral Genetic Material

Although some phages and most plant viruses are RNAviruses, the broadest variety of RNA genomes is found amongthe viruses that infect animals. Among the three types of single-stranded RNA genomes found in animal viruses, thegenome of class IV viruses can directly serve as mRNA andthus can be translated into viral protein immediately after infection. Figure 19.7 shows a virus of class V, in which the RNA

genome serves as a template for mRNA synthesis. The RNAgenome is transcribed into complementary RNA strands,which function both as mRNA and as templates for the synthesis ofadditional copies ofgenomic RNA. All viruses that require RNA • RNA synthesis to make mRNA use a viralenzyme capable of carrying out this process; there are no suchenzymes in most cells. The viral enzyme is packaged with thegenome inside the viral capsid.

The RNA animal viruses with the most complicated reproductive cycles are the retroviruses (class VI). These virusesare equipped with an enzyme called reverse transcriptasc,which transcribes an RNA template into DNA, providingan RNA ---+ DNA information flow, the opposite of the usualdirection. This unusual phenomenon is the source of thename retroviruses (retm means "backward"). Of particularmedical importance is HIV (human immunodeficiency virus),the retrovirus that causes AIDS (acquired immunodeficiencysyndrome). HIV and other retroviruses are enveloped virusesthat contain two identical molecules of single-stranded RNAand two molecules of reverse transcriptase.


OReversetranscriptasecatalyzes thesynthesis of asecond DNAstrand complementary to thefirst

~The doublestranded DNAis incorporatedas a provirusinto the cell'sDNA.

OReverse transcriptasecatalyzes the synthesis ofa DNA strand complementary to the viralRNA.

.The viral proteinsinclude capsid proteinsand reverse transcriptase (made in the cytosol) and envelope glycoproteins (made in the ER),

9Vesicles transport theglycoproteins to the cell'splasma membrane,

G)Capsids areassembled aroundviral genomes andreverse transcriptasemolecules.

... Figure 19.8 The reproductive cycle of HIV, the retrovirusthat causes AIDS. Note in step 4 that DNA synthesized from the viralRNA genome IS integrated into the host cell chromosomal DNA, acharacteristic unique to retroviruses The photos on the left (artificiallycolored TEMs) show HIVentering and leaving a human while blood cell,

DNA NVVV>A.NVVV>A) NU(lEUS

~~rovirus (JProviral

Chromosomal J genes areDNA transcribed into

RNA molecules,

"I+--~---------r-.j which serve asRNA genome ./ I~ genomes forfor the ~ the next viralnext viral fVVVVV\ "'Q"g generation andgeneration J mRNA IV\IVVV\A. ..'"""~ as mRNAs for

, "translation intoviral protein,

, ~ "tI \1.,.0:·.... ,l>~1."- .... '..... ,~....

RNA-DNAhybrid

Viral RNA

,,>~'tU".....:" '"~

::\ --"w' /;,-t;,-~...:- S

L'·lE)New viruses budoff from the host cell.

RNA (twoidentical

...... ... strands)Reverse "~"~transcriptase ••• '\

HIV

)

The virus fuses with the~t!t~ cell's plasma membrane.~ ..~ The capsid proteins aret4 removed, releasing the.. viral proteins and RNA.

';1 ::~U.,-..; -.-,,-.: \. ......

~., (_ • A.' II HOST Ell••• 'U:1En.·

••• :: ~Reverse~ transcriptase

~

Membrane ofwhite blood cell

IHIV

HIV entering a cell

New HIV leaving a cell

o The envelopeglycoproteins enable the

virus to bind to specific1---~fYreceptors on certain

white blood cells.

Figure 19,8 traces the HIV reproductive cycle, which is typical of a retrovirus. After HIV enters a host cell, its reversetranscriptase molecules are released into the cytoplasm, wherethey catalyze synthesis ofviral DNA. The newly made viral DNAthen enters the cell's nucleus and integrates into the DNA of a

chromosome. The integrated viral DNA, called a provirus,never leaves the host's genome, remaining a permanent residentof the cell. (Recall that a prophage, in contrast, leaves the host'sgenome at the start ofa lytic cycle.) The host's RNA polymerasetranscribes the proviral DNA into RNA molecules, which can

CIlAPTE~ NINHHN Viruses 389

CONCEPT CHECK

function both as mRNA for the synthesis of viral proteins and asgenomes for the new viruses that will be assembled and releasedfrom the ceiL In Chapter43, we describe how HIV causes the de~

terioration of the immune system that occurs in AIDS.

Evolution of Viruses

We began this chapter by asking whether or not viruses are alive.Viruses do not really fit our definition of living organisms. Anisolated virus is biologically inert, unable to replicate its genes orregenerate its own supply of ATP. Yet it has a genetic programwritten in the universal language oflife. Do we think ofviruses asnature's most complex associations of molecules or as the simplest forms of life? Either way, we must bend our usual definitions. Although viruses cannot reproduce or carry out metabolicactivities independently, their use of the genetic code makes ithard to deny their evolutionary connection to the living world.

How did viruses originate? Viruses have been found that in~

fect every fonn of life-not just bacteria, animals, and plants, butalso archaea, fungi, and algae and other protists. Because theydepend on cells for their own propagation, it seems likely thatviruses are not the descendants of precellular forms of life butevolved after the first cells appeared, possibly multiple times.Most molecular biologists favor the hypothesis that viruses originated from naked bits ofcellular nucleic acids that moved fromone cell to another, perhaps via injured cell surfaces. The evolution of genes coding for capsid proteins may have facilitated theinfection of uninjured cells. Candidates for the original sourcesofviral genomes include plasmids and transposons. Plasmids aresmall, circular DNA molecules found in bacteria and in the uni~

cellular eukaryotes called yeasts. Plasmids exist apart from thecell's genome, can replicate independently of the genome, andare occasionally transferred between cells. Transposonsare DNAsegments that can move from one location to another within acell's genome. Thus, plasmids, transposons, and viruses all sharean important feature: TIley are mobilegenetic elements. We willdiscuss plasmids in more detail in Chapters 20 and 27 and transposons in Chapter 21.

Consistent with this vision of pieces of DNA shuttling fromcell to cell is the observation that a viral genome can have morein common with the genome of its host than with the genomesof viruses that infect other hosts. Indeed, some viral genes areessentially identical to genes ofthe host. On the other hand, re~

cent sequencing of many viral genomes has shown that the ge~

netic sequences of some viruses are quite similar to those ofseemingly distantly related viruses; for example, some animalviruses share similar sequences with plant viruses. This geneticsimilarity may reflect the persistence of groups of viral genesthat were favored by natural selectionduring the earlyevolutionofviruses and the eukaryotic cells that served as their hosts.

The debate about the origin ofviruses has been reinvigoratedrecently by reports of mimivirus, the largest virus yet discovered. Mimivirus is a double-stranded DNA virus with an icosa-


hedral capsid that is 400 nm in diameter. (The beginning of itsname is short for mimicking microbe because the virus is thesize ofa small bacterium.) Its genome contains 1.2 million bases(about lOOtimes as many as the influenza virus genome) and anestimated 1,000 genes. Perhaps the most surprising aspect ofmimivirus, however, is that some ofthe genes appear to code forproducts previously thought to be hallmarks of cellulargenomes. These products include proteins involved in translation, DNA repair, protein folding, and polysaccharide synthesis.The researchers who described mimivirus propose that it mostlikely evolved before the first cells and then developed an exploitative relationship with them. Other scientists disagree,maintaining that the virus evolved more recently than cells andhas simply been efficient at scavenginggenes from its hosts. Thequestion of whether some viruses deserve their own earlybranch on the tree of life may not be answered for some time.

The ongoing evolutionary relationship between virusesand the genomes oftheir host cells is an association that makesviruses very useful experimental systems in molecular biology.Knowledge about viruses also has many practical applications,since viruses have a tremendous impact on all organismsthrough their ability to cause disease.

19.21. Compare the effect on the host cell of a lytic (virulent)

phage and a lysogenic (temperate) phage.2. How do some viruses reproduce without possessing

or ever synthesizing DNA?3. Why is HIV called a retrovirus?4.•~J:t."IDI If you were a researcher trying to com

bat HIV infection, what molecular processes couldyou attempt to block? (See Figure 19.8.)

For suggested answers. see Appendix A.

r~;;~'s::~ v~~;:s, and prions areformidable pathogens in animalsand plants

Diseases caused by viral infections afflict humans, agriculturalcrops, and livestock worldwide. Other smaller, less complexentities known as viroids and prions also cause disease inplants and animals, respectively.

Viral Diseases in Animals

A viral infection can produce symptoms by a number of different routes. Viruses may damage or kill cells by causing therelease of hydrolytic enzymes from lysosomes. Some virusescause infected cells to produce toxins that lead to disease

symptoms, and some have molecular components that aretoxic, such as envelope proteins. How much damage a viruscauses depends partly on the ability of the infected tissue toregenerate by cell division. People usually recover completely

from colds because the epithelium of the respiratory tract,

which the viruses infect, can efficiently repair itself. In contrast, damage inflicted by poliovirus to mature nerve cells ispermanent, because these cells do not divide and usually cannot be replaced. Many of the temporary symptoms associatedwith viral infections, such as fever and aches, actually result

from the body's own efforts at defending itself against infection rather than from cell death caused by the virus.

The immune system is a complex and critical part of thebody's natural defenses (see Chapter 43). It is also the basis forthe major medical tool for preventing viral infectionsvaccines. A vaccine is a harmless variant or derivative of apathogen that stimulates the immune system to mount defenses against the harmful pathogen. Smallpox, a viral disease

that was at one time a devastating scourge in many parts of theworld, was eradicated by a vaccination program carried out bythe World Health Organization. The very narrow host rangeof the smallpox virus-it infects only humans-was a criticalfactor in the success of this program. Similar worldwide vaccination campaigns are currently under way to eradicate polioand measles. Effective vaccines are also available againstrubella, mumps, hepatitis B, and a number of other viraldiseases.

Although vaccines can prevent certain viral illnesses, medical technology can do little, at present, to cure most viral infections once they occur. The antibiotics that help us recoverfrom bacterial infections are powerless against viruses. An

tibiotics kill bacteria by inhibiting enzymes specific to bacteria but have no effect on eukaryotic or virally encodedenzymes. However, the few enzymes that are encoded byviruses have provided targets for other drugs. Most antiviraldrugs resemble nucleosides and as a result interfere with viralnucleic acid synthesis. One such drug is acyclovir, which impedes herpesvirus reproduction by inhibiting the viral polymerase that synthesizes viral DNA. Similarly, azidothymidine(AZT) curbs HIV reproduction by interfering with the synthesis of DNA by reverse transcriptase. In the past twodecades, much effort has gone into developing drugs againstHI\!: Currently, multidrug treatments, sometimes called"cocktaiJs,~ have been found to be most effective. Such treat

ments commonly include a combination of m'o nucleosidemimics and a protease inhibitor, which interferes with an enzyme required for assembly of the viruses.

Emerging VirusesViruses that appear suddenly or are new to medical scientistsare often referred to as emerging viruses. HIV, the AIDS virus,is a classic example: This virus appeared in San Francisco in

the early 1980s, seemingly out of nowhere, although laterstudies uncovered a case in the Belgian Congo that occurredas early as 1959. The deadly Ebola virus, recognized initially in1976 in central Africa, is one of several emerging viruses that

cause hemorrhagicfever, an often fatal syndrome (set ofsymptoms) characterized by fever, vomiting, massive bleeding, and

circulatory system collapse. A number of other dangerousemerging viruses cause encephalitis, inflammation of thebrain. One example is the West Nile virus, which appeared inNorth America for the first time in 1999 and has spread to all48 contiguous states in the United States.

Severe acute respiratory syndrome (SARS) first appeared insouthern China in November 2002. A global outbreak that occurred during the follOWing eight months infected about 8,000people and killed more than 700. Researchers quickly identified the infectious agent as a coronavirus, a virus with a single·stranded RNA genome (class IV) that had not previously been

known to cause disease in humans. Public health workers responded rapidly, isolating patients and quarantining thosewho had come in contact with them. Because of low infectivity and other characteristics of the SARS virus, this rapid response succeeded in quelling the outbreak before it couldinfect a much larger population.

How do such viruses burst on the human scene, giving riseto harmful diseases that were previously rare or even unknown? Three processes contribute to the emergence of viraldiseases. The first, and perhaps most important, is the mutation of existing viruses. RNA viruses tend to have an unusually high rate of mutation because errors in replicating theirRNA genomes are not corrected by proofreading. Some mu

tations change existing viruses into new genetic varieties(strains) that can cause disease, even in individuals who are

immune to the ancestral virus. For instance, general outbreaks of flu, or flu epidemics, are caused by new strains ofinfluenza virus genetically different enough from earlierstrains that people have little immunity to them.

A second process that can lead to the emergence of viraldiseases is the dissemination of a viral disease from a small,isolated human population. For instance, AIDS went unnamed and virtually unnoticed for decades before it began tospread around the world. In this case, technological and socialfactors, including affordable international travel, blood transfusions, sexual promiscuity, and the abuse of intravenous

drugs, allowed a previously rare human disease to become aglobal scourge.

A third source of new viral diseases in humans is the spreadof existing viruses from other animals. Scientists estimate thatabout three-quarters of new human diseases originate in thisway. Animals that harbor and can transmit a particular virusbut are generally unaffected by it are said to act as a naturalreservoir for that virus. For example, a species of bat has beenidentified as the likely natural reservoir of the SARS virus. Batsare sold as food in China, and their dried feces are even sold

CHAPTER NINETEEN Viruses 391

.. Figure 19.9 Influenza in humans and other animals.

(a) The 1918 flu pandemic. Many of those infeded were treated inlarge makeshift hospitals. such as this one.

been exposed to that particular strain before, humans will lackimmunity, and the recombinant virus has the potential to behighly pathogenic. If such a flu virus recombines with viruses

that circulate widely among humans, it may acquire the ability

to spread easily from person to person, dramatically increasing the potential for a major human outbreak.

Different strains of influenza A are given standardizednames; for example, the strain that caused the 1918 flu is calledHINL The name identifies which forms of two viral surfaceproteins are present: hemagglutinin (H) and neuraminidase(N). There are 16 different types of hemagglutinin, a proteinthat helps the flu virus attach to host cells, and 9 types of neuraminidase, an enzyme that helps release new virus particlesfrom infected cells. Water birds have been found that carryviruses with all possible combinations of Hand N.

In 1997, at least 18 people in Hong Kong were infectedwith an HSNI virus (Figure 19.9b); six of these people subsequently died. The same strain, previously seen only in wildbirds, had killed several thousand chickens earlier that year,

presumably passed along from wild birds or other species. Amass culling of all of Hong Kong's 1.5 million domestic birdsappeared to stop that outbreak. Beginning in 2002, however,new cases ofH5N1 human infection began to crop up aroundsoutheast Asia. By 2007, the disease caused by this virus, nowcalled ~avian flu,u had killed about 160 people. Perhaps even

more alarming is the overall mortality rate, which is greaterthan 50%. More than 100 million birds have either died fromthe disease or been killed to prevent the spread of infection;efforts are under way to vaccinate birds of several species(Figure 19.9c).

The geographical and host ranges of avian flu virus continue

to expand. It has shown up in wild or domestic birds in Africaand Europe, as well as in pigs, tigers, and domestic cats anddogs. The expanding host range provides increasing opportunities for different strains of virus to reassart their genetic material and for new strains to emerge. If the HSNI avian flu virusevolves so that it can spread easily from person to person, itcould bring about a major human outbreak. Human-to-humantransmission is strongly suspected in several cases where thedisease has clustered in families, but so far the disease has notspread beyond small groups to cause an epidemic. For thosestudying emerging viruses and their ability to give rise to a human pandemic, avian flu provides a sobering lesson in progress.

As we have seen, emerging viruses are generally not new;rather, they are existing viruses that mutate, disseminate morewidely in the current host species, or spread to new hostspecies. Changes in host behavior or environmental changescan increase theviraI traffic responsible for emerging diseases.For example, new roads through remote areas can allowviruses to spread between previously isolated human populations. Also, the destruction of forests to expand cropland canbring humans into contact with other animals that may hostviruses capable of infecting humans.

e(l Vaccinating ducks. Veterinariansadminister ~accinalions in aregion of China reporting cases ofavian flu. caused by strain H5Nl

.. ~• • 0.5 pm

....

(bl Influenza A H5N1 virus.Virus particles are seenbudding from an infededcell in this colorized TEM.

for medicinal uses; either of these practices could provide aroute for transmission of the virus to humans.

Flu epidemics provide an instructive example of the effectsof viruses moving between species. There are three types of

influenza virus: types Band C, which infect only humans andhave never caused an epidemic, and type A, which infects a

wide range of animals, including birds, pigs, horses, and humans. Influenza A strains have caused three major flu epidemics among humans in the last l00years. The worst was theuSpanish flu~ pandemic (a global epidemic) of 1918-1919,

which killed about 40 million people, including many WorldWar I soldiers (Figure 19.9a). Evidence points to birds as thesource of the 1918 flu pandemic.

A likely scenario for that pandemic and others is that theybegan when the virus mutated as it passed from one hostspecies to another. When an animal is infected with more than

one strain offlu virus, the different strains can undergo geneticrecombination if the RNA molecules making up theirgenomes mix and match during viral assembly. Coupled withmutation, these changes can lead to the emergence of a viralstrain that is capable of infecting human cells. Having never


Viral Diseases in Plants

More than 2,000 types of viral diseases of plants are known,and together they account for an estimated annual10ss 0£$15billion worldwide due to their destruction of agricultural andhorticultural crops. Common signs of viral infection includebleached or brown spots on leaves and fruits, stunted growth,and damaged flowers or roots, all tending to diminish theyield and quality of crops (Figure 19.10).

Plant viruses have the same basic struchtre and mode of reproduction as animal viruses. Most plant viruses discovered thusfar, including tobacco mosaic virus (TMV), have an RNAgenome. Many have a helical capsid, like TMV (see Figure 19.3a);others have an icosahedral capsid.

Viral diseases of plants spread by two major routes. In thefirst route, called horiwntaltransmission, a plant is infe<tedfrom an external source of the virus. Because the invadingvirus must get past the plant's outer protective layer of cells(the epidermis), a plant becomes more susceptible to viral infections if it has been damaged by wind, injury, or herbivores.Herbivores, especially insects, pose a double threat becausethey can also act as carriers of viruses, transmitting diseasefrom plant to plant. Farmers and gardeners may transmit plantviruses inadvertently on pruning shears and other tools. Theother route of viral infection is vertical transmission, in whicha plant inherits a viral infection from a parent. Vertical transmission can occur in asexual propagation (for example, cuttings) or in sexual reproduction via infected seeds.

Once a virus enters a plant cell and begins reproducing, viral genomes and associated proteins can spread throughout theplant by means of plasmodesmata, the cytoplasmic conne<tions that penetrate the walls bern'een adjacent plant cells (see

... Figure 19.10 Viralinfection of plants.Infection with particular virusescauses irregular brown patches on tomatoes (left),black blotching on squash (center), and streaking intulips due to redistribution of pigment granules (right)

Figure 6.28). The passage of viral macromole<ules from cell tocell is facilitated by virally encoded proteins that cause enlargement of plasmodesmata. Scientists have not yet devised curesfor most viral plant diseases, Consequently, their efforts are focused largely on reducing the transmission of such diseasesand on breeding resistant varieties ofcrop plants.

Viroids and Prions:The Simplest Infectious Agents

As small and simple as viruses are, they dwarf another class ofpathogens:viroids. Thesearecircular RNA molecules, onlyafewhundred nucleotides long, that infect plants. Viroids do not encode proteins but can replicate in host plant cells, apparently using host cell enzymes. These small RNA mole<ules seem to causeerrors in the regulatory systems that control plantgrowth, and thetypical signs of viroid diseases are abnormal development andstunted growth. One viroid disease, called cadang-cadang, haskilled more than 10 million coconut palms in the Philippines.

An important lesson from viroids is that a single moleculecan be an infectious agent that spreads a disease. But viroids arenucleic acid, whose ability to be replicated is well known. Evenmore surprising is the evidence for infectious proteins, calledprioRS, which appear to cause a number of degenerative braindiseases in various animal species. These diseases includescrapie in sheep; mad cow disease, which has plagued the European beef industry in recent years; and Creutzfeldt-Jakob disease in humans, which has caused the death ofsome 150 peoplein Great Britain over the past decade. Prions are most likelytransmitted in food, as may occur when people eat prion-ladenbeef from cattle with mad cow disease. Kuru, another humandisease caused by prions, was identified in the early 19(X)s

among the South Fore natives of NewGuinea, Akuru epidemic peaked there inthe 1960s, puzzling scientists, who at firstthought the disease had a genetic basis.Eventually, however, anthropological investigations ferreted out how the diseasewas spread: ritual cannibalism, a widespread practice among South Fore natives at that time.

Two characteristics of prions are especially alarming. First, prions act veryslowly, with an incubation period of atleast ten years before symptoms develop.The lengthy incubation period preventssources of infection from being identified until long after the first cases appear,allowing many more infections to occur.Second, prions are virtually indestructible; they are not destroyed or deactivatedby heating to normal cooking temperatures. To date, there is no known cure for


GAggregatesof pnons

.. Figure 19.11 Model for how prionspropagate. Prions are mis/olded versions ofnormal brain proteins. When a prion contactsa normally folded version of the same protein,It may indl.lce the normal protein to assl.lmethe abnormal shape, The resulting chainreaction may continue until high levels ofprion aggregation cause cellular malfunctionand eventual degeneration of the brain.

I. Describe two ways a preexisting virus can become anemerging virus.

2. Contrast horizontal and vertical transmission ofviruses in plants.

3. TMV has been isolated from virtually all commercialtobacco products. Why, then, is TMV infection notan additional hazard for smokers?

4. _Mtnl. How might the HSNI avian fluvirus have spread from Asia to Africa and Europe?Is it likely that human air travel could havespread this virus? How could you test yourhypothesis?

For suggested answers, see Appendix A.

prion diseases, and the only hope for developing effective treatments lies in understanding the process of infection.

How can a protein, which cannot replicate itself, be a transmissible pathogen? According to the leading model, a prion isa misfolded form of a protein normally present in brain cells.When the prion gets into a cell containing the normal form ofthe protein, the prion somehow converts normal protein mol~

ecules to the misfolded prion versions. Several prions then ag~

gregate into a complex that can convert other normal proteinsto prions, which join the chain (Figure 19.11). Prion aggregation interferes with normal cellular functions and causesdisease symptoms. This model was greeted with muchskepticism when it was first proposed by Stanley Prusiner inthe early 198Os, but it is now widely accepted. Prusiner wasawarded the Nobel Prize in 1997 for his work on prions.

CONCEPT CHECK 19.3

r;;'1 I.CSi~l~.iZ'·I.1 Go to the Study Area at www.masteringbio.comfor6ioFlix--' 3-D Animations, MP3 Tutors, Videos. Practi<e Tests, an e600k, and more.

SUMMARY OF KEY CONCEPTS

synthesize progeny viruses. Each type of virus has a characteristic host range,

.. Reproductive Cycles of Phages Phages (viruses that infectbacteria) can reproduce by two alternative mechanisms: thelytic cycle and the lysogenic cycle,

L)"logenic cycle• Temperate phage only• Genome integr~tes into bacterial

chromosome ~s prophage, which(I) is replicated and passed on tod~ughter cells ~nd

W Cil/1 be Induced to le~ve the chromosome and InitIate a lytiC cycle

.',11'.,,- 19.1Avirus consisls of a nucleic acid surrounded by aprotein coat (pp. 381-384).. The Discovery of Viruses: Scientific Inquiry Researchers

discovered viruses in the late 1800s by studying a plant disease, tobacco mosaic disease.

.. Structure of Viruses Avirus is a small nucleic acid genomeenclosed in a protein capsid and sometimes a membranousenvelope containing viral proteins that help viruses enter cells.The genome may be single~ or double·stranded DNA or RNA.

••,1'''''-19.2Viruses reproduce only in host cells (pp. 384-390).. General Features of Viral Reproductive Cycles Viruses

use enzymes, ribosomes, and small molecules of host cells to


lytic cycle• Virulent or temper~te ph~ge

• Destruction ot host DNA• ProdlKtion ot new phages• L~I of host cell C~Use5 rele~se

of progeny ph~ges

Elac:terr~1

chromosome \

-M4if.•Acthity Simplified Viral Reproductive Cycle

Acthity Phage Lytic Cycle

Acthity Phage Lysogenic and Lytic Cycles

Actl\'lty Retrovirus (HIV) Reproductive C)"Cle

• ',11""-19.3Viruses, viroids, and prions are formidable pathogensin animals and plants (pp. 390--394).. Viral Diseases in Animals Symptoms may be caused by

direct viral harm to cells or by the body's immune response.Vaccines stimulate the immune system to defend the hostagainst specific viruses.

... Emerging Viruses Outbreaks of "new" viral diseases in humans are usually caused by existing viruses that expand theirhost territory. The H5Nl avian flu virus is being closely monitored for its potential to cause a serious flu pandemic.

.. Viral Diseases in Plants Viruses enter plant cells throughdamaged cell walls (horizontal transmission) or are inheritedfrom a parent (vertical transmission).

.. Viroids and Prions: The Simplest Infectious AgentsViroids are naked RNA molecules that infect plants and disrupt their growth. Prions are slow-acting, Virtually indestructible infectious proteins that cause brain diseases in mammals.

-M4It.•Investigation What C~uses Infections in AIDS Patients'

In...·stigation Why Do AIDS Rates Differ Aero.. the U.s.?

TESTING YOUR KNOWLEDGE

SELF·QUIZ

I. A bacterium is infected with an experimentally constructed

bacteriophage composed ofthe 1'2 phage protein coat and T4

phage DNA. The new phages produced would have

a. 1'2 protein and T4 DNA.

b. 1'2 protein and T2 DNA.

c. a mixture of the DNA and proteins of both phages.

d. 14 protein and T4 DNA.

e. 14 protein and T2 DNA.

2. RNA viruses require their own supply ofcertain enzymes because

a. host cells rapidly destroy the viruses.

b. host cells lack enzymes that can replicate the viral genome.c. these enzymes translate viral mRNA into proteins.

d. these enzymes penetrate host cell membranes.

e. these enzymes cannot be made in host cells.

3. Which of the follOWing characteristics, structures, or processes

is common to both bacteria and viruses?

a. metabolism

b. ribosomes

c. genetic material composed of nucleic acid

d. cell division

e. independent existence

4. Emerging viruses arise by

a. mutation of existing viruses.

b. the spread of existing viruses to new host species.

c. the spread of existing viruses more widely within their

host species.

d. all of the above

e. none of the above

5. To cause a human pandemic, the H5Nl avian flu virus would

have to

a. spread to primates such as chimpanzees.b. develop into a virus with a different host range.

c. become capable of human-to-human transmission.

d. arise independently in chickens in North and South

America.

e. become much more pathogenic.

6. "P.,I,I'iI Redraw Figure 19.7 to show the reproductive cy

cle of a virus with a single-stranded genome that can function

as mRNA (a class IV virus).

For Self·Quiz answers, see Appendix A.

-$14 if·. ViSit the Study Area at www.masteringbio.com lor aPractice Test

EVOLUTION CONNECTION

7. The success of some viruses lies in their ability to evolve rapidly

within the host. Such a virus evades the host's defenses by mu

tating and producing many altered progeny viruses before the

body can mount an attack. Thus, the viruses present late in in

fection differ from those that initially infected the body. Dis

cuss this as an example of evolution in microcosm. Which viral

lineages tend to predominate?

SCIENTIFIC INQUIRY

8. When bacteria infect an animal, the number of bacteria in the

body increases in an exponential fashion (graph A). After infec

tion by a virulent animal virus with a lytic reproductive cycle,

there is no evidence of infection for a while. Then, the number

of viruses rises suddenly and subsequently increases in a series

of steps (graph B). Explain the difference in the curves.

t A •.~ •••2• ,D

'0 '0" "•• DD EE, ,z z

Time Time

Biological Inquiry: A Workbook ofln"eitigati\"e (aiei Explore West Nilevirus in the case "The Dunor's Dilemma,· E"I'lore the immune response to nupathogens with the c~se ·P~ndemic Flu (Past and Possible)."

CHAPTER NINETEEN Viruses 395