Viruses and Prions

Viruses and PrionsChapter 14

14.1 Structure and Classification of Animal VirusesStructure

DNA or RNA genome

Double stranded (ds) or single stranded (ss)

Surrounded by a capsid (protein coat)

The nucleic acid and capsid are termed nucleocapsid

Some viruses have an envelope

The envelope is a phospholipid bilayer membrane that was obtained from the cell in which the virus arose

Viruses are obligate intracellular parasites

They occur in many shapes, some of which are distinctive

14.1 Structure and Classification of Animal Viruses

14.1 Structure and Classification of Animal Viruses

Humanpapillomavirus

Rhabdovirus Ebola virus

Viral genomes exhibit a range of complexity

Polioviruses: single-stranded RNA virus

Herpesviruses: double-stranded DNA

Retroviruses: diploid single-stranded RNA

Influenza viruses: multiple gene segments of single-stranded RNA

Genome sizes

Hantaviruses have 3 genes that encode 4 polypeptides

Pox viruses have nearly 200 genes

There are thousands of known viruses (and probably tens of thousands of unknown viruses)

14.1 Structure and Classification of Animal Viruses

14.1 Structure and Classification of Animal Viruses

Virus Classification

Genome structure

Virus particle structure

Presence or absence of an envelope

Nomenclature rule: Viruses are named for the geographic region in which they are discovered

14.1 Structure and Classification of Animal Viruses

14.1 Structure and Classification of Animal Viruses

Groupings by Transmission Mechanism

Enteric viruses: fecal-oral route

Respiratory viruses: aerosols

Zoonotic agents

Biting

Respiratory route

Sexually-transmitted

14.1 Structure and Classification of Animal Viruses

14.1 Structure and Classification of Animal Viruses

14.2 Interactions of Animal Viruses and Their Hosts

Viruses tend to be species- and cell-specific

Infection is a 9-step process

Attachment

Entry

Targeting to site of viral replication

Uncoating

Nucleic acid replication and protein synthesis

Maturation

Release from cells

Shedding from host

Transmission to other hosts

Step 1: Attachment

Mediated by cell-surface molecule(s) and viral spike proteins

HIV gp120 is specific for CD4

CD4 is principally found on helper T cells

Occurs by noncovalent interactions

14.2 Interactions of Animal Viruses and Their Hosts

14.2 Interactions of Animal Viruses and Their Hosts

Step 2: Entry into the cell

Some viruses fuse with the cell’s plasma membrane

HIV’s gp41 interacts with a cellular chemokine receptor to induce fusion

Other viruses are internalized by endocytosis

In either case, the capsid, containing the nucleic acid and viral enzymes, is dumped into the cytoplasm

14.2 Interactions of Animal Viruses and Their Hosts

14.2 Interactions of Animal Viruses and Their Hosts

14.2 Interactions of Animal Viruses and Their Hosts

14.2 Interactions of Animal Viruses and Their Hosts

Step 3: Targeting to the site of viral replication

Most DNA viruses replicate in the nucleus

Most RNA viruses replicate in the cytoplasm

Some viruses integrate their dsDNA into the host cell’s genome (i.e., chromosomes)

Some viruses copy their RNA into dsDNA, which is then integrated into the host cell’s genome

14.2 Interactions of Animal Viruses and Their Hosts

14.2 Interactions of Animal Viruses and Their Hosts

Step 4: Uncoating

The capsid is composed of protein subunits

The nucleic acid dissociates from the subunits

This causes the capsid to disintegrate, liberating the nucleic acid

14.2 Interactions of Animal Viruses and Their Hosts

14.2 Interactions of Animal Viruses and Their Hosts

Step 5: Nucleic acid replication and protein synthesis

RNA viruses

Some RNA virus genomes act as a mRNA (”plus-strand” viruses)

All others (minus-strand viruses) possess a prepackaged, virus-encoded RNA-dependent RNA polymerase

DNA viruses encode RNA polymerases

Many viruses have polycistronic mRNAs

Viral polypeptides are synthesized by the cell’s translational machinery

14.2 Interactions of Animal Viruses and Their Hosts

14.2 Interactions of Animal Viruses and Their Hosts

Step 6: Maturation

Cleavage of polycistronic polypeptides into subunits

HIV gp160 polypeptide is cleaved into its gp120 and gp41 mature polypeptides

This step is inhibited by the HIV protease inhibitors taken by HIV+ patients

Nucleic acids and capsid proteins spontaneously polymerize into nucleocapsid

14.2 Interactions of Animal Viruses and Their Hosts

14.2 Interactions of Animal Viruses and Their Hosts

Step 7: Release from cells

Some viruses rely upon cell lysis for release into the extracellular environment

Other viruses rely upon budding, whereby they exit from the cell, taking part of its membrane (viral envelope)

Budding occurs at the plasma membrane, ER or Golgi, depending on the viral species

If the rate of budding exceeds the rate of membrane synthesis, then the cell will die

Step 8: Shedding from the host

Viruses must leave the infected host to infect other hosts

Shedding can be a minor event (such as cold viruses) or a catastrophic event (such as hemorrhagic fever viruses)

Step 9: Transmission to other hosts

Transmission routes usually reflect the sites of infection for viruses (e.g., respiratory, GI, STD)

14.2 Interactions of Animal Viruses and Their Hosts

14.2 Interactions of Animal Viruses and Their Hosts

14.2 Interactions of Animal Viruses and Their Hosts

14.2 Interactions of Animal Viruses and Their Hosts

Persistent infections

Latent - periods of inactivation and activation (e.g., herpesviruses); usually limited pathology

Chronic - infectious virus can be detected for years or decades with little discernible pathology, but can eventually lead to disease (e.g., hepatitis B and C viruses)

Slow infections - short period of acute infection (weeks) followed by the apparent disappearance of virus for months or years, with pathology ensuing (e.g., HIV)

14.3 Viruses and Human TumorsTumor viruses drive cell proliferation

Several mechanisms account for this phenomenon

Viral oncogenes that stimulate cell proliferation

Viral DNA integrates adjacent to genes that drive cell division

Expression of the viral genes leads to aberrant expression of the cellular gene

Some viruses encode growth factors that stimulate cellular proliferation

Epstein-Barr virus encodes viral interleukin-10 that causes B cell proliferation, leading to Burkitt’s lymphoma

14.4 Viral Genetic AlterationsSegmented viruses contain multiple genetic elements that encode different genes

Influenza viruses are the best characterized of segmented viruses

The gene sequences of these segments within the same species can vary, thus provide genetic diversity

Coinfection of a cell with two or more different strains of a virus, such as influenza A viruses, can lead to the emergence of reassortant viruses that have distinct characteristics

The process is termed reassortment

Influenza A viruses have 8 gene segments that encode 10 polypeptides

Segment 1 (2,341 nt): PB2

Segment 2 (2,341 nt): PB1

Segment 3 (2,233 nt): PA

Segment 4 (1,778 nt): HA (hemagglutinin) - 16 known subtypes

Segment 5 (1,565 nt): NP

Segment 6 (1,413 nt): NA (neuraminidase) - 9 known subtypes

Segment 7 (1,027 nt): M1, M2

Segment 8 (890 nt): NS1, NS2

14.4 Viral Genetic Alterations14.4 Viral Genetic Alterations

The H5N1 influenza virus has subtype 5 HA segment and subtype 1 NA segment

14.5 Methods Used to Study Viruses

Cultivation of host cells

Embryonated chicken eggs

Must be susceptible to the virus

Two principal targets

Chorioallantoic fluid (CAF)

Embryo

14.5 Methods Used to Study Viruses

14.5 Methods Used to Study Viruses

Cell culture

Cells must be susceptible to virus

Cells are grown attached to flasks in a monolayer

Cells are inoculated with virus

Within days, cytopathic effect (CPE) can be seen

14.7 Other Infectious AgentsPrions

Proteinaceous infectious particle

Cause spongiform encephalopathies

Characteristics

They contain no nucleic acids

They are a normal cellular protein (PrPc) that has misfolded into a pathogenic protein

The prion protein “replicates” itself by causing copies of the normal protein to misfold into the prion protein

Diseases

Creutzfeldt-Jakob (New Variant CJ from “mad” cows)

Kuru (religious consumption of brains from deceased)

Chronic wasting disease (elk, deer, moose)