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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

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14 1 structure and classification of animal viruses
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
14 1 structure and classification of animal viruses1
14.1 Structure and Classification of Animal Viruses
  • Viruses are obligate intracellular parasites
  • They occur in many shapes, some of which are distinctive

Human

papillomavirus

Rhabdovirus

Ebola virus

14 1 structure and classification of animal viruses2
14.1 Structure and Classification of Animal Viruses
  • 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 viruses3
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 viruses4
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 2 interactions of animal viruses and their hosts
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
slide8
14.2 Interactions of Animal Viruses and Their 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 hosts1
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 hosts2
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 hosts3
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 hosts4
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 hosts5
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 hosts6
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
14 2 interactions of animal viruses and their hosts7
14.2 Interactions of Animal Viruses and Their Hosts
  • 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 hosts8
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
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
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
14 4 viral genetic alterations1
14.4 Viral Genetic Alterations
  • 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

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

14 5 methods used to study viruses
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 viruses1
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
14.7 Other Infectious Agents
  • Prions
    • Proteinaceous infectious particle
    • Cause spongiform encephalopathies
    • Characteristics
      • They contain no nucleic acids
      • They are a normal cellular protein (PrPc) that has misfoldedinto 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)
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