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Blueboom/Virus

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Viruses

General characterisics

  • infectious agents
  • acellular
  • require hosts for replication
  • termed obligate intracellular parasites


  • exploit machinery of host cell
  • possess no ribosomes nor ATP generating systems
  • replicate independently of host cell chromosome

Virus definition

a subcellular agent consisting of a core of nucleic acid surrounded by a protein coat that must use the metabolic machinery of a living host to replicate and produce more viral particules

Viron

A term for complete infectious viral particle (extracellular form)

Size

  • ultramicroscopic- smallest infectous agent <.2micrometers)
  • require electron microscope to visualize
  • animal viruses largest .4 microm in length
  • smallest .02 microm diameter

Viral ultra structure

  • composition is simple by diverse varying in size shape and chemical composition
  • has a covering and a central core
  • covering -capsid and envelope(but not in all viruses)
  • central core - nucleic acid and various proteins
  • capsid found in all viruses
  • capsid protects the genome
  • protein shell surrounds nucleic acid sometimes referred to as nucleocapsid (capsid and nucleic acid)
  • composed of identifcal individual protein molecules known as protomers
  • protomers organize aggregate themselves into capsosmers polypeptides

**advantage: reduces the need for excessive genetic information and promotes self assembly requiring no ATP or additional enzymes there are two types of capsid symmetry helical and icosahedral

Helical Capsid

  • a viron with helical symmetry appears rod shaped . Capsomers are arranged into a coild -> helix 3d shape
  • diameter is determined by size and packaging of the protomers
  • length is determined by length of NA

Iscosahedral capsid

  • a viron with icosahedral symmetry appears approximately spherical
  • shape and dimensions depend on protomers (3d)
  • in general a 20 sided polygon (12 spaced corners with a capsomer at each corner) with two capsomer types
  • triangular hexons composes the flat faces of 6 capsomers
  • round pentons compose the corners of 5 capsomers
  • there are variable capsomer #'s
  • poliovirus 32 (12 pentons , 20 hexons) adenovirus 252 (12 pentons , 240 hexons)

Capsid function

  1. provides the nucleic acid protection from digestion by enzymes
  2. contains special sites on its surface allowing attachment of the virion to a host cell
  3. provides proteins that enable the virion to penetrate the host cell membrane
  4. in some to inject the infectious nucleic acid into the cell's cytoplasm

Viral envelope

  • surrounds nucleocapsid of many viruses but not all
  • a protein phospholiipid layer of unique composition
  • lipids from host cell membrane
  • proteins are virus specific modified viral proteins not host membrane proteins

note sensitivity

  • presence of an envelope makes the viral particle sensitive to lipid dissolving agents (ether) dessication (influcenting survival time in the environment) detergents acids etc

envelope -> adds instability

Types of envelope proteins

  • matrix proteins link envelope to capsid
  • stabilize virus and mediates interaction between capsid proteins and envelope
  • surface proteins exposed capsid proteins or envelope
  • glycoproteins sometimes reffered to as spikes or peplomers
  • requred for attachement of virus to host cell (antigenic determinants)

Example of exposed surface proteins

  • influenza virus has 2 types
  • haemagglutinin (surface glycoprotein)
  • attaches to sialic acid residues of host cell surface, agglutinates RBCs
  • Neuroaminidase (surface spike) dissolves neuraminic acid (cytoplasmic membrane of mammalian cells) aids in releasing virus from host cell
  • please note not all virusses possess an envelope
  • if lacking - virus is termed a naked virus as opposed to an enveloped virus

Nucleoprotein core

  • viral nucleic acid (NA) - this is either DNA or RNA but not both
  • viral genomes are small
  • largest known bacteriophage - 670kbp
  • note bacteria 1000-5000kbp
  • some genomes are so small that they only contain 4 genes (hep b virus) .. herpes contains hundreds
  • Is so small becuses viruses use host cell's nucleic acid and protein and energy so only need genes to encode for proteins of own envelope , capsid and nucleoprotein core

Viral genome types

  • there are a variety of viral genome types

dna viruses (either double ds or single stranded)

  • most we deal with are double stranded
  • for example
    • poxviridae
    • herpesviridae
    • adenoviridae
    • hepadnaviridae
    • papoviridae and polymaviruses

Rna viruses

  • learn mostly single stranded ones
  • positive (+) stranded rna - genomes of the same polarity as mRNA
  • ie Picornaviridae and calciviridae
  • Negative (-) stranded RNA genomes of opposite polarity to mRNA
  • ie Rhabdoviridae
  • Unique Ambisense genomes (both positive and negative stranded RNA)
  • ie arenaviridae and bunyaviridae

nucleoproteins

  • found within the core
  • stabilize nucleic acid during replication or have enzymatic function
  • majority required for replication strategies

Polymerases (synth of dna 7 rna)

  • dna -dependent RNA polymerase (poxvirus)
  • RNA dependent DNA polymerase (RNA tumor viruses)
  • RNA dependent RNA polymerase (RNA viruses)

Reverse transcriptase

DNA copy from RNA genome (HIV)

VIRAL classification

ICTV standards

  1. type of nucleic acid
  2. symmetry of capsid
  3. presence/absense of envelope
  4. size of virus particle

Baltimore system

  • production of mRNA during infection
  • compliments ICTV
  • viral replication strategies
  • placement of viruses in 7 arbitrary groups

Class I double stranded DNA

  • some replicate in nucleus
  • some replicate in cytoplasm

Class II single stranded(+) sense DNA

  • replications occurs in the nucleus
  • formation of (-) sense strand
  • serves as template for +strand RNA and DNA synthesis

Class III double stranded RNA

  • have segmented genomes
  • each genome segment transcribed separately to produce monocistronic mRNAs

Class IV single stranded + sense RNA

Polycistronic mRNA
  • hep A genome RNA = mRNA
  • naked RNA is infectious , no viron particle associated polymerase
  • translation-> formation of polyprotein product
  • cleaved to form mature proteins
Complex transcription
  • two or more rounds of translation necessary to produce genomic RNA

Class V single stranded - sense RNA

  • must have viron particle RNA directd RNA polymerase
Segmented
  • first step transcription of (-) sense rna genome by viron RNA dependant RNA polymerase to produce monocistronic mRNAs
  • serve as the template for genome replication
Non-segmented
  • as above monocistronic mRNA are produced

Class VI Single stranded + sense RNA with DNA intermediate in life cycle (retroviruses)

  • genome + sense but unique doploid)

vdoes not serve as mRNA but as template for reverse transcription

ClassVII double stranded DNA with RNA intermediate

  • relies on reverse transcription
  • occurs inside particle on maturation
  • on infection of new cell
  • first event is repair of gapped genome then transcription

Viral multiplication

  1. Adsorption attachment
  2. Penetration
  3. Uncoating
  4. Replication of macromolecules (DNA,RNA and Proteins)
  5. Assembly of viral structural components
  6. Release of mature virus from the host

Adsorption

aka Attachment

  • virus comes at specific binding site of suseptible host cell.
  • Must be aligned
  • Attachment is instantaneous

Penetration

  1. Endocytosis- Energy dependant. Naked and Enveloped viruses may be endocytosed by host cell into an endocytic vesicle which releases the viral capsid into the cell cytoplasm
  2. Fusion - Membrane enveloped fusion . most viruses use this.

Uncoating

  • involves removal of viral proteins
  • preparation for transcription/translation

Transcription and/or Translation

synthesis of viral mRNA and translation of viral proteins from new mRNA or parental RNA (transfecting viruses)

Replication

newly synthesized proteins (DNA or RNA dependant polymerases) initiate steps for viral genome biosynthesis

Assembly/Maturation

  • assembly of structural proteins and genome into virions happens:
    • in cytosol (RNA virus except orthomyxovirus)
    • or in nucleus (DNA viruses except Pox virus)

Viral Replication

  • primary cells -taken directly from host and grown. may be diluted and placed into new flasks which would be classified as secondary cells
  • Transformed cells when cells are suceptible but non permissve to dna containing viruses
  • you see changes in
    • morphology (rounder)
    • physiology (increased multiplication)
    • behavior (lose contact inhibition)
  • potential to cause tumors in small mammals

Single step replication

Two phases

Eclipse phase

  • after infection of cells, virus enters host, uncoats itself.
    • virus cannot be seen or recovered from infected cell
  • phase ends when first virus particle is observed inside the infected cell

Latent phase

  • time elapsed between the start time to the appearance of first new extracellular virus
  • virus accumulates inside the infected cell ready to be released into the medium
  • ends when virus is seen extracellularly
  • Eclipse phase is included in latent phase

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This page was last modified on 16 March 2008, at 19:55.
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