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Genes and Genomics > Virology > Flashcards

Virology Flashcards

1
Q

Virus Definition

A

a small non cellular agent consisting largely of nucleic acid within a protein coat requiring a host cell for replication
- not considered alive

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2
Q

Virus vs. Life Form

A

Virus:

  1. no metabolism
  2. multiple origins
  3. assembly
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3
Q

Viral Genome Diversity

A
  1. DNA or RNA
  2. double or single stranded
  3. circular or linear
  4. +/- sense
  5. segmented or nonsegmented
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4
Q

Virion particle

A

an entire virus particle, consisting of an outer protein shell called a capsid and an inner core of nucleic acid
- is infectious

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5
Q

DNA vs RNA Genomes

A
  • DNA viruses often larger in genome size because of the proofreading enzyme ability
  • RNA is less stable
  • overlapping genes common
    eg. HIV-1 has 4 genes in different reading frames
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6
Q

Double or single stranded

A
  • most RNA viruses are ss (except reoviruses)
  • regions of dsRNA and intracomplementarity within the strand
  • most DNA viruses are ds as this is more stable
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7
Q

Circular or linear

A
  • most are linear
  • circular viruses often in phages
  • DNA viruses can be circularized for a period in the life cycle
  • circular viruses will be persistent in the cell (replicated)
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8
Q

Negative sense viruses

A

3’-5’

  • copy to make + sense mRNA for translation
  • make into 5’-3’ direction for host cell translation
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9
Q

Positive sense viruses

A

5’-3’

- can be directly translated by host into progeny

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10
Q

Non-segmented vs Segmented

A

non-segmented: mono-partite

segmented: multipartite
eg. retroviruses have + sense non-segmented genome

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11
Q

Influenza Virus

A
  • ve sense segmented genome
  • genome encoded on little ‘chromosomes’ with 1/2 proteins
  • evolves by mutation, recombination (within single piece of genome), or reassortment
  • reassortment is the exchange of entire segments for another virus
  • antigenic shift: RNA segments exchanged between viral strains in secondary host (no cross protective immunity to novel virus)
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12
Q

Virus structure

A
  • genome surrounded by capsid protein coat
  • The core confers infectivity, and the capsid provides specificity to the virus
  • sometimes you get a host lipid envelope
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13
Q

Tobacco Mosaic Virus

A

+ sense RNA

  • capsid protecting the RNA core
  • 4 capsid proteins replicated in the cell
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14
Q

Capsids

A
  • assembly of monomeric protein units can produce spherical particles
  • gives shape and structure
  • auto-assembly without host help
  • many symmetrical possibilities which affect host cell binding
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15
Q

Ebolavirus

A
  • some viruses have an envelope in addition to a capsid
  • capsid differentiated
  • lipid membrane derived from host
  • envelope proteins on the surface bind to the host membrane receptor proteins
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16
Q

Viral Hosts

A
  • some viruses are host specific (smallpox or polio)
  • eradication possible because of a lack of a reservoir
  • reservoir hosts: natural infected animal/may not be symptomatic
  • vector: animal transmitting disease
  • dead end host: virus in host not sufficient for transfer back to mosquito
    eg West Nile Virus in birds
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17
Q

Mimivirus

A
  • related to other viruses
  • may represent a new ‘life form’
  • large genome size (900 genes) and physical size
  • produce virion factories
  • ‘alive’ in the way a seed is
18
Q

Steps in Viral Replication

A
  1. infection and disassembly of infectious particle
    - uncoating of nucleic acid core
  2. replication of viral genome
  3. synthesis of viral proteins by host machinery
    - transcription/translation
  4. reassembly into progeny virus particles + maturation
    - burst exit from cell
    - genome specific
19
Q

Replication Phases

A
  • eclipse phase: enter host and start takeover (low viral load)
  • maturation and release phase
  • decay phase: virus doesn’t survive as virion particles
20
Q

Host Cell Attachment

A
  • recognise cellular receptors of cell surface

- determines which cells can be infected

21
Q

HIV-1 Receptors

A
  • retrovirus
  • recognises 2 receptors
  • can switch receptors during infection (macrophages vs T cells)
  • this is called cellular tropism
22
Q

Host Cell Infection/Disassembly

A
  • fusion or endocytosis

- uncoating (disassembly)

23
Q

HIV Infection

A

Enveloped:

  • fusion and uncoating of virus injects RNA into cell
  • leaves envelope on surface
  • binding triggers conformational change for fusion
24
Q

Influenza Infection

A

RNA:

  • binds to cell surface
  • induces cell endocytosis and virus inside endosome
  • cell pumps in H+ (acidification) and this causes conformational change, fusion, and uncoating
  • nucleic acid in cytoplasm
25
Q

Poliovirus Infection

A

RNA:

  • no envelope = no fusion
  • binds to receptor
  • binding causes complex series of event ending in viral RNA moved through pore in vesicle
26
Q

Adenovirus Infection

A

DNA:

  • endocytosis and lysis of vesicle
  • nuclear localisation signal on capsid surface locating to nuclear pore
27
Q

Genome Replication

A
  • DNA viruses replicate in the nucleus (except poxvirus)
  • RNA viruses replicate in cytoplasm (except retroviruses)
  • produces polypeptide that is cleaved by proteases
28
Q

ssRNA (+) replication

A
  • negative strand RNA synthesis: positive strand RNA synthesis : forms virion particle
  • host cell translation of initial positive sense RNA into capsid proteins and RNA pol/dep that synthesize -/+ sense RNA for formation of virus
29
Q

ssRNA (-) replication

A
  • need an RNA dependent RNA polymerase
  • virion particle contains virion polymerase attached to RNA
  • RNA dep/pol synthesizes positive RNA from negative strand
  • positive sense RNA is translated into more viral polymerase/capsids
  • also made back into negative RNA by virion polymerase for formation of new virus particles
30
Q

dsDNA replication

A
  • need insertion into nucleus
  • DNA replication (host or viral) for new virus particles
  • DNA transcription (inside nucleus) and translation (outside nucleus) into capsids/DNA pol
  • assembly in nucleus at site of DNA replication
31
Q

retrovirus replication

A
  • carry reverse transcriptase to make DNA out of RNA
  • integrate into the genome
  • in nucleus, reverse transcriptase goes from RNA to dsDNA
  • integration
  • transcription and translation from genome
  • synthesis of reverse transcriptase, RNA, and capsid
  • formation of virus particle
32
Q

Host proteins and virus replication

A
  • transcription often uses host polymerases
  • host TF bind to viral RNA to control expression
  • translation uses host ribosomes
  • polypeptides cleaved with host proteases
33
Q

Virus Assembly

A
  • capsid assembly generally occurs at site of genome replication (often self assembly with simultaneous binding of viral genome to capsid protein)
  • viruses with envelopes are assembled either on cell surface or in sub-cellular compartments
  • viral membrane derived from host cell
34
Q

Retrovirus surface assembly

A

1) no envelope: lyse cell
2) envelope: lyse or bud
- capsid containing viral chromosome
- nucelocapsid induces assembly of transmembrane envelope proteins
- budding off and formation of progeny virus

35
Q

Smallpox subsurface assembly

A
  • replicate in viral factories with different morphologies
    IMV: efficient at new host infection ; 2 membranes/needs lysis
    EEV: infect other cells in same organism (longe range spread) ; 3 membranes/exocytosis
    CEV: induces actin tail from cell to deposit CEV onto short range neighbour cell)
36
Q

Types of Viral Infections

A
  • permissive: cells supporting viral infections
  • productive infection leads to cytopathic effects if acute
  • infection of non permissive cells leads to abortive infection where host cell stops replication
  • a persistent infection is chronic
  • viruses can transform cells via abortive infection or oncogenesis (cause mutations and damage or turn on/insert oncogene)
37
Q

Host Cell Morphological Changes

A
  • nuclear inclusion
  • cytoskeleton
  • giant cell formation
  • syncytia: fusion of viral envelope with uninfected cells to make giant cells
38
Q

Host Cell Biochemical Changes

A
  • activation of cellular protein kinases/TFs
  • activation of oncogenes/cell cycle arrest
  • inhibition of DNA synthesis
39
Q

Host Cell Defences

A
  • induced defenses

- non-induced defenses

40
Q

Induced Defenses

A
  • interferon stimulation of cells causes ‘viral state’
  • infection upregulates production in cells
  • warns uninfected cells to turn on defences
  • targets points in viral replication cycle by inducing protein production
    1. transcription inhibitors
    2. translation inhibitors
    3. protein processing inhibitor
    4. virus maturation inhibitor
41
Q

Translation Inhibitory Protein

A
  • recognises cap snatching from hist mRNA

- slows ribosome speed to stop viral RNA production

42
Q

Retrovirus Transformation

A
  • isolated from chicken fivrosarcoma
  • is a tranforming virus causing cancer
  • generated when cellular protooncogene captured by insertion into viral genome during viral replication
  • can then be passed on to further hosts
  • oncogene is Src protein tyrosine kinase: virus didn’t capture bit cells use to turn this kinase ‘off’
  • oncogene beneficial to virus as it causes cell growth

Genes and Genomics (13 decks)

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