Viruses and prions
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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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Viruses and Prions

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Viruses and prions

Viruses and Prions

  • Chapter 14


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


Viruses and prions

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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