Viruses and Prions Chapter 14

14.1 Structure and Classification of Animal Viruses Structure 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 Human papillomavirus RhabdovirusEbola 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

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

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

14.2 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

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

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 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 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 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 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

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 Tumors Tumor 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 Alterations Segmented 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, NS 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 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 Agents Prions Proteinaceous infectious particle Cause spongiform encephalopathies Characteristics They contain no nucleic acids They are a normal cellular protein (PrP c ) 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)