Viruses, viroids, and prions - Napa Valley College · Viruses, viroids, and prions Chapter 13 BIO 220 Fig. 13.1 Characteristics of viruses • Very, very small (filterable) • Obligatory

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Viruses, viroids, and prions

Chapter 13

BIO 220

Fig. 13.1

Characteristics of viruses

• Very, very small (filterable)

• Obligatory intracellular parasite

• Viruses are composed of a nucleic acid, a

protein coat , sometimes an envelope

• Viruses produce few (if any) enzymes

• Parasitize host cell for building materials like

amino acids, lipids, and nucleotides

• Without the host cell, viruses can not carry

out “life”-sustaining processes

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Host range of virus

• Spectrum of host cells virus can invade

• Most viruses can only infect specific types of cells of only one host species

• Range determined by

– Virus must be able to interact with specific receptor sites on host cell surface (i.e. cell wall, plasma membrane, part of fimbriae or flagella)

– Availability within the specific host of cellular factors necessary for viral multiplication

Why do we care about viruses?

• They causes illness and disease

• Maybe we can use them to treat disease

– Phage therapy

• An alternative to antibiotics?

– Oncolytic viruses

Viral structure

• Viruses are composed of a nucleic acid surrounded by a protein coat called a capsid

• Some viruses have a lipid/protein/CHO envelope surrounding the capsid

• A virion is a complete, fully developed, infectious viral particle located outside a host cell

Nucleic acids

• Virus can have DNA or RNA

• Nucleic acid can be ds or ss

• Nucleic acid may be a few thousand nucleotides up to 250,000 nucleotides

• Nucleic acid may be circular or linear

• For some viruses, the percentage of nucleic acid in relation to protein is about 1% (influenza), can be up to 50% (certain bacteriophages)

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Capsid

• This is the protein coat covering the viral

nucleic acid

• Protein subunits of capsid are called

capsomeres

• Functions:

– Protection

– Contains attachment sites

– Proteins allow viral

penetration of host cell

Fig. 13.2

Envelopes

• Nonenveloped viruses lack an envelope

• Enveloped viruses do have an envelope

• Some viral capsids are covered by envelopes which may be made of lipids, proteins, and/or CHOs

– May be a result of extrusion from host cell

– Viral nucleic acid codes for envelope proteins, other components derived from the host cell

• Some envelopes may be covered in spikes (CHO/protein complexes)

Spikes

• May be means of attachment to host cells

• May be used as a means of identification

Fig. 13.3

Influenza

• HA spikes (hemagglutinin spikes)

– Binds sialic acid on host cell membranes

– Mediates fusion between virus and host cell membrane

– Main antigenic sites on virus

• NA spikes (neuraminidase spikes)

– Enable virus to be released from host cell

– Target of drugs like Tamiflu and Relenza

• Spikes can be used for identification of subtypes of the virus

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Influenza classification

• A – infects humans and several types of

animals (i.e. birds, horses, swine)

• B – humans

• C – humans, less frequently swine and dogs

• D – cattle

• Influenza pandemics are caused by Type A

viruses, which are classified into subtypes

based on the HA and NA spikes

• HA (17 versions), NA (10 versions)

Viruses are tricky

• Some viruses have evolved mechanisms for

evading antibodies (that were produced in

response to that particular virus)

– Viral genes, including those determining viral

surface proteins, are susceptible to mutation

– The progeny of mutant viruses therefore have

altered surface proteins (slight changes in spikes),

which are not recognized by the antibodies

– Antigenic drift – a gradual, continuous change

Antigenic shift

• A major change in the virus that

results in new combinations of

HA spikes or HA and NA proteins

• Can take place when a human or

animal is infected with two

different subtypes of virus

• Reassortment of nucleic acids

can result in a modified virus that

humans do not have immunity to

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Viral morphology

Based on capsid architecture

• Helical (rabies, Ebola)

• Polyhedral (adenovirus, poliovirus)

• Enveloped (influenza)

• Complex

– Bacteriophages

Fig. 13.5a

Fig. 13.4a

Classification of viruses

• Way people imagined they were contracted or symptomology

• Scientists that discovered them

• Based on disease they produce

• Animal/tissue affinity

• Host range or specificity

• Morphological characteristics

– Type of nucleic acid/enveloped or naked/capsid size/capsid architecture

Viral species

• A group of viruses sharing the same genetic

information and ecological niche (host range)

• No specific epithets

• Designated by descriptive common names,

with subspecies designated by a number

How can we grow viruses in the lab to

study them?

For animal viruses . . .

• Grow virus in live animals

• Chicken embryos

• Cell/tissue culture

Bacteriophages

• Much easier to grow in lab

Figs. 13.7 & 13.8

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Plaque method (Bacteriophages)

Fig. 13.6

Theoretically, each plaque corresponds to a single virus in the initial suspension.

Viral multiplication

• The virion nucleic acid contains only a few genes for the synthesis of new virus

– Genes for viral structural components

– Genes for some of the enzymes used in viral life cycle (i.e. replicating viral nucleic acid)

– Some virions contain a few preformed enzymes

– Genes are only transcribed and proteins made if virus is in host cell

• Most everything else is supplied by host cell

Viral one-step growth curve

Fig. 13.10

Bacteriophage multiplication

• The lytic cycle

• The lysogenic cycle

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Virulent phages

• Undergoes the lytic cycle

• The result of the lytic cycle is viral replication

and death of the host cell as mature virions

are released

• T-even bacteriophages

Phage lysozyme

Degradation host DNA

Viral mRNA transcribed/translated

Phage components synthesized

Lysozyme

Fig. 13.11

Temperate phages aka lysogenic phages

• Can undergo a lytic or lysogenic cycle, depending on environmental conditions

• In the lysogenic cycle the phage DNA is incorporated into the bacterial chromosome

– “Prophage” is inactive during this period

• The phage DNA can be excised via induction and then enter the lytic cycle

Fig. 13.12

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Consequences of lysogeny

• Lysogenic cells are immune to reinfection by the

same phage

• Phage conversion – host cell may exhibit new

properties, i.e. toxin production

– Corynebacterium diphtheriae, Clostridium botulinum

• Specialized transduction is possible

– When a prophage is excised from its host

chromosome, it can take with it a bit of the adjacent

DNA from the bacterial chromosome

Fig. 13.13

The type of nucleic acid as well as whether or not the virus has an envelope

will determine the life cycle of an animal virus.

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Multiplication of animal viruses

• Attachment

• Entry

• Uncoating

• Biosynthesis of virus

• Maturation and release

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Multiplication of animal viruses

• Attachment

– Animal viruses have attachment sites that bind to

receptor sites on host cell PM

• Entry

– Many viruses enter by receptor-mediated

endocytosis

– Fusion (enveloped viruses)

Fig. 13.14

Multiplication of animal viruses

• Uncoating

– This is the step where the capsid is removed from

the viral nucleic acid

• Host lysosomal enzymes

• Enzymes encoded by viral DNA that are

synthesized soon after infection

– Location of uncoating depends on virus

Biosynthesis of DNA viruses

• Generally, DNA viruses replicate their DNA in the host cell nucleus by using viral enzymes

• Capsid synthesis in cytoplasm by using host cell enzymes

• Virion assembly in nucleus

• Virions transported to PM for release via ER

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Fig. 13.15

Papovavirus – naked, dsDNA

Viral DNA enter nucleus,

Transcription of early genes

carried out by host RNA pol

After replication of viral DNA has

begun, transcription/translation

of “late” genes occurs

Biosynthesis of RNA viruses

• Virus multiplies in cytoplasm

• Viral RNA codes for RNA-dependent RNA

polymerase, which makes a complementary

copy of RNA

Fig. 13.17

+RNA virus (ss), naked

Picornaviridae (poliovirus, enterovirus)

Viral RNA translated, resulting

proteins (1) (-) synthesis of

host RNA, (2) RNA-dependent

RNA polymerase

Antisense strands serve as template for

making more sense RNA, Sense strand

serves as RNA template, translated,

inserted in capsid

Zika virus

• ss +RNA virus, enveloped

• Member of flaviviridae

• Transmitted by Aedes mosquitos, but sexual transmission is also possible

• Zika fever symptoms include headache, fever, maculopapular rash, and conjunctivitis, but symptoms vary

– Can cause a birth defect called microcephaly

– Can also cause Guillain-Barre syndrome in adults

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Detection and treatment

Detection

• PCR (detection of viral RNA)

• Presence of antibodies in serum

Treatment

• None

• Vector control!

– Wolbachia

Fig. 13.17-RNA virus (ss), enveloped

Antisense RNA can’t be used as

mRNA, so RNA-dependent RNA

polymerase a part of the virion

Sense RNA a template for more antisense

RNA production & also translated, Antisense

RNA packaged into capsids, template for

sense RNA

Biosynthesis of RNA viruses that use DNA

Fig. 13.19

Retroviruses & oncogenic RNA viruses

Original viral RNA degraded

Virus may remain

in a latent state or

may be expressed,

but is not removed

from chromosome

Capsids contain

reverse transcriptase,

integrase, protease

HIV

• A retrovirus (Lentivirus)

• Two strands of +RNA

• Reverse transcriptase

• Phospholipid envelope

with gp120 spikes

• Spread by dendritic cells

• Activated CD4+ cells are

main target

Fig. 19.13

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HIV infection of target T cells

Fig. 19.13

Infection in CD4+ cells

Fig. 19.14

Infection in APCs

Fig. 19.15

How is HIV able to persist?

• Integrated in host genome as provirus

• Virus may not be released by infected cells

(stored as latent virions in vacuoles)

• Some infected cells become a reservoir for the

virus

• Cell-cell fusion

• Rapid antigenic changes due to reverse

transcriptase activity (high mutation rate)

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HIV subtypes

• HIV-1

– Most virulent

– Accounts for 99% of cases

– Related to viruses in western Africa that affect primates

– Further subdivided by letter . . .

• HIV-2

– Related to virus that affects the sooty mangabeys

– Not common outside of Africa

– Patients may be asymptomatic for lengthy periods

Fig. 19.16

Acquired Immunodeficiency Syndrome

(AIDS)

• Final stage of human immunodeficiency virus

(HIV) infection

• Patients susceptible to infections due to

suppressed immune activity

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HIV detection

• ELISA (detection of HIV antibodies)

• Western blots

• Real-time PCR

HIV transmission

• Blood

• Semen

• Intimate sexual contact

• Breast milk

• Transplacental

• Blood-contaminated needles

• Organ transplants

• Artificial insemination

• Blood transfusion

Drugs that inhibit the HIV life cycle

Fig. 19.18

Multiplication of animal viruses

• Attachment

• Entry

• Uncoating

• Biosynthesis of virus

• Maturation and release

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Maturation and release

• Capsid is assembled

• Nucleocapsid forms

• Naked viruses cause rupture of the host cell

• Enveloped viruses often leave the host cell via

a process called budding

– Envelope proteins are encoded by viral genes and

are inserted in host cell PM

– Envelope forms as virion leaves the host

Budding

Fig. 13.20

Transformation of normal cells into cancer

cells

• Can be due to viruses

• Cancer-inducing genes (oncogenes) carried by viruses are actually derived from animal cells

• Oncogenes can be activated to abnormal functioning by a variety of factors

• Oncogenic viruses can induce tumor formation

– Virus integrates into host cell DNA and replicates along with the host cell DNA, ultimately transforming host cell

• After being transformed by viruses, tumor cells contain a virus-specific antigen on their cell surface (tumor-specific transplantation antigen (TSTA) or in the nucleus (T antigen)

DNA oncogenic viruses

• Adenoviridae

• Herpesviridae

– Epstein-Barr virus

• Poxviridae

• Papovaviridae

– Human papillomaviruses

• Hepadnaviridae

– Hepatitis B

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RNA oncogenic viruses

• Retroviridae

– T-cell leukemia virus

– Feline leukemia virus

Viruses to treat cancer

• Adenovirus (H101) – head/neck/lung cancer

• Talimogene laherparepvec (T-VEC) - melanoma

• Reolysin

• Delta 24 cold virus – brain cancer

• Modified measles – myeloma

• Modified herpesvirus

• Modified HIV - leukemia

Viral infections

• A latent viral infection is one in which the virus

remains quiet or latent within a host cell and

does not produce disease for an extended

period, perhaps years

– i.e. Varicella-zoster virus

• Persistent viral infections occur gradually over

an extended period of time

– Usually fatal

Latent and persistent viral infections

Fig. 13.21

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Prions

• Proteinaceous infectious particle

• Cause diseases such as kuru, Creutzfeldt-Jakob

disease, fatal familial insomnia, mad cow

disease, and scrapie which are neurological

diseases called spongiform encephalopathies

• Disease is caused by the conversion of a

normal host glycoprotein (PrPC) into an

infectious form (PrPSc)

Fig. 13.22

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Plant viruses and viroids

• Plant viruses are morphologically similar to animal viruses and have similar types of nucleic acids

• Because of the presence of the plant cell walls, viruses typically gain access through wounds or are assisted by other parasites (nematodes, fungi, insects)

• Some plant diseases are caused by viroids, which consist of naked RNA