Saturday, February 7, 2009

Overview of Viruses and Virology
Chapter 10
I. Virus Structure and Growth

10.1 General Properties of Viruses

 Virus: genetic element that cannot replicate independently of a living (host) cell
 Virology: the study of viruses
 Virus particle: extracellular form of a virus; allows virus to exist outside host and facilitates transmission from one host cell to another
 Virion: the infectious virus particle; the nucleic acid genome surrounded by a protein coat and, in some cases, other layers of material
 Viral Genomes
 Either DNA or RNA genomes
 Some circular, but most linear
 Viral Hosts and Taxonomy
 Viruses can be classified on the basis of the hosts they infect
 Bacterial viruses (bacteriophages)
 Animal viruses
 Plant viruses

10.2 Nature of the Virion

 Most viruses are smaller than prokaryotic cells; range from 0.02 to 0.3 µm
 Most viral genomes are smaller than those of biological cells
 Viral Structure
 Capsid: the protein shell that surrounds the genome of a virus particle
 Composed of a number of protein molecules arranged in a pattern
 Capsomer: subunit of the capsid
 Smallest morphological unit visible with an electron microscope
 Nucleocapsid: complete nucleic acid and protein packaged in the virion
 Enveloped virus: virus that contains layers around the nucleocapsid
 Nucleocapsids of viruses constructed in highly symmetric ways
 Helical symmetry: rod-shaped viruses (e.g., tobacco mosaic virus)
 Length of virus determined by length of nucleic acid
 Width of virus determined by size and packaging of protein subunits
 Icosahedral symmetry: spherical viruses
 Most efficient arrangement of subunits in a closed shell

 Enveloped Viruses
 Have membrane surrounding nucleocapsid; lipid bilayer with embedded proteins
 Make initial contact with host cell
 Complex Viruses
 Virions composed of several parts, each with separate shapes and symmetries
 Bacterial viruses contain icosahedral heads and helical tails
 Some virions contain enzymes critical to infection
 Lysozyme
 Nucleic acid polymerases
 Neuraminadases: enzymes that cleave gycosidic bonds/freeviruses from host

10.3 The Virus Host

 Viruses replicate only in certain types of cells or in whole organisms
 Bacterial viruses are typically easiest to grow; model systems
 Animal viruses (and some plant viruses) can be cultivated in tissue or cells

10.4 Quantification of Viruses

 Titer: number of infectious units per volume of fluid
 Plaque assay: analogous to the bacterial colony
 Plaques are clear zones that develop on lawns of host cells
 Each plaque results from infection by a single virus particle


II. Viral Replication

10.5 General Features of Virus Replication
 The Phases of Viral Replication
 Attachment (adsorption) of the virus to a susceptible host cell
 Entry (penetration) of the virion or its nucleic acid
 Synthesis of virus nucleic acid and protein by cell as redirected by virus
 Assembly of capsids and packaging of viral genomes into new virions
 Release of mature virions from host cell
 Virus replication typically characterized by a one-step growth curve
 Latent period: eclipse + maturation
 Burst size: number of virions released

10.6 Viral Attachment and Penetration

 Attachment of virion to host cell is highly specific
 Requires complementary receptors on the host and its infecting virus
 Receptors on host cell carry out normal functions for cell
 Receptors include proteins, carbohydrates, glycoproteins, lipids etc.
 The viral attachment results in changes to virus and cell surface
 Permissive cell: cell that allows complete viral replication cycle
 Bacteriophage T4: Virions attach to cell via tail fibers
 Tail fibers retract and tail core makes contact with E. coli cell wall
 Lysozyme-like enzyme forms small pore in peptidoglycan
 Tail sheath contracts and viral DNA passes into cytoplasm
 Many eukaryotes possess mechanisms to diminish viral infections
 E.g., immune defense mechanisms, RNA interference
 Many bacteria employ restriction-modification systems to evade infection
 DNA destruction system; only effective against double-stranded DNA viruses
 Restriction enzymes (restriction endonucleases) cleave DNA
 Viral mechanisms to evade bacterial restriction systems
 Chemical modification of viral DNA (glycosylation or methylation)
 Production of proteins that inhibit host cell restriction system

10.7 Production of Viral Nucleic Acid and Protein

 Once a host has been infected, new copies of the viral genome must be made and virus-specific proteins synthesized in order for the virus to replicate
 Generation of messenger RNA (mRNA) occurs first
 Typically viral genome serves as template for viral mRNA
 In some RNA viruses, viral RNA itself is the mRNA
 In some cases essential transcriptional enzymes are contained in the virion

 Nomenclature used to describe mRNA is used to describe the configuration of the genome of a single-stranded DNA or RNA virus (mRNA is said to be in plus (+) configuration; its complement is in minus (-) configuration)

 Positive-strand RNA virus: single-stranded RNA genome with same orientation as its mRNA
 Negative-strand RNA virus: single-stranded RNA genome with complementary orientation as its mRNA
 Retroviruses: animal viruses responsible for causing certain types of cancers and acquired immunodeficiency syndrome (AIDS)
 Require reverse transcriptase

 Viral Proteins
 Production follows synthesis of viral mRNA
 Early proteins
 synthesized soon after infection
 necessary for replication of virus nucleic acid
 typically act catalytically
 synthesized in smaller amounts

 Production of Viral Proteins (cont’d)
 Late proteins
 Synthesized later
 Include proteins of virus coat
 Typically structural components
 Synthesized in larger amounts

III. Viral Diversity

10.8 Overview of Bacterial Viruses

 Bacteriophages are very diverse
 Best-studied bacteriophages infect enteric bacteria
 E.g., E. coli, Salmonella enterica
 Most contain dsDNA genomes
 Most are naked, but some possess lipid envelopes
 They are structurally complex, containing heads, tails and other components

 Viral Life Cycles
 Virulent mode: viruses lyse host cells after infection
 Temperate mode: viruses replicate their genomes in tandem with host genome and without killing host

10.10 Temperate Bacteriophages Temperate viruses: can undergo a different life cycle resulting in a stable genetic relationship within the host
 But can also kill cells through lytic cycle
 Lysogeny: state where most virus genes not expressed and virus genome is replicated in synchrony with host chromosome
 Lysogen: a bacterium containing a prophage
 Under certain conditions lysogenic viruses may revert to the lytic pathway

10.11 Overview of Animal Viruses
 Unlike prokaryotes, entire virion enters the animal cell
 Eukaryotic cells contain a nucleus, the replication site for animal viruses
 Animal viruses contain all known modes of viral genome replication
 Many more kinds of enveloped animal viruses than bacterial viruses exist
 Animal viruses can use part of host cell’s membrane for envelope

 Consequences of Virus Infection in Animal Cells
 Persistent infections: release of virus from host doesn't = cell lysis
 Infected cell remains alive and continues to produce virus indefinitely
 Latent infections: delay between infection by the virus and lytic events
 Transformation: conversion of normal cell into tumor cell

10.12 Retroviruses

 Retroviruses: RNA viruses that replicate through a DNA intermediate
 Enveloped viruses
 Contain a reverse transcriptase (copies info from its RNA genome into DNA)

 Process of Replication of a Retrovirus
 Entrance into the cell
 Removal of virion envelope at the membrane
 Reverse transcription of one of the two RNA genomes
 Integration of retroviral DNA into host genome
 Transcription of retroviral DNA
 Assembly and packaging of genomic RNA
 Budding of enveloped virions; release from cell

IV. Subviral Entities

10.13 Defective Viruses

 Helper viruses (defective viruses): parasitic on other viruses
 Satellite viruses: defective viruses for which no intact version exists; rely on unrelated viruses as helpers

10.14 Viroids

 Viroids: infectious RNA molecules that lack a protein coat
 Small, circular, ssRNA molecules
 Smallest known pathogens (246–399 bp)
 Cause a number of important plant diseases
 Do not encode proteins; completely dependent on host-encoded enzymes

10.15 Prions
 Prions: infectious proteins whose extracellular form contains no nucleic acid
 Known to cause disease in animals (transmissible spongiform encephalopathies)
 Host cell contains gene (PrnP) that encodes native form of prion protein  Prion misfolding results in neurological symptoms of disease
 Prion disease occurs by three distinct mechanisms
 Sporadic prion disease: random misfolding of a normal, healthy prion protein  Inherited prion disease: mutation in prion gene yields a protein that changes more often into disease-causing form

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