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MICR3320 > 3 - Viral Genetics > Flashcards

3 - Viral Genetics Flashcards

1
Q

Forms that viral genomes exist in

A
  • DNA, RNA (mainly), DNA with short segments of RNA
  • Double stranded, single stranded (+) stand, (-) strand, or ambisense
  • Linear, circular, segmented, continuous, gapped
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2
Q

All viral genomes must encode gene products and regulatory signals required for…

A
  • Genome replication
  • Assembly and packaging of the genome
  • Expression and regulatory signals
  • Modulation of cell defences and propagation to other cells
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3
Q

Viral genomes

A
  • Encode some, never all of the proteins required to complete viral replication
  • All RNA viruses must encode either an RNA dependent RNA polymerase or a reverse transcriptase for efficient replication
  • Both lack proof reading activity and contribute to viral diversity
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4
Q

How many replication strategies exists for all known viruses

A

Seven

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5
Q

Baltimore classification

A
  • Based on the type of nucleic acid genome and replication strategy
  • All must produce mRNA that can be translated by cellular ribosomes to produce viral structural protein
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6
Q

mRNA

A

Defined as + strand because it contains immediately translatable information

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7
Q

RNA dependent RNA polymerase (RdRp)

A
  • Essential protein encoded in the genomes of all RNA containing viruses with no DNA stage
  • Cells do not have ability to replicate viral RNA genomes or to synthesise mRNA from viral RNA
  • VIral RdRp synthesizes mRNA which is readable by cellular ribosomes
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8
Q

Baltimore classification groups

A
  • Group 1: dsDNA
  • Group 2: ssDNA
  • Group 3: dsRNA
  • Group 4: RNA (+)
  • Group 5: RNA (-)
  • Group 6: RNA (+, RT)
  • Group 7: dsDNA (RT)
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9
Q

Group 1

A
  • +/- dsDNA
    Enzymes required:
  • DNA-dependent DNA Polymerase (DdDp)
  • DNA-dependent RNA Polymerase (DdRp)
  • Viral dsDNA synthesized with DdDp
  • Viral mRNA synthesized with DdRp (viral
    protein translated)
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10
Q

Examples of group 1 viruses

A
  • Herpesviruses
  • Papillomavirus
  • Polyomavirus
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11
Q

Group 2

A
  • (+) ssDNA
    Enzymes required for replication:
  • Cellular DdDp (forms +ssDNA after dsDNA)
  • Cellular DdRp (forms viral mRNA)
  • RNA can only be synthesized from dsDNA, complementary DNA has to be synthesised first, to convert genome to dsDNA
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12
Q

Uses for newly synthesized viral dsDNA

A

Used as template to synthesise:
- +viral mRNA: translated to viral protein
- Ss(+) viral DNA genome

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13
Q

Examples of group 2 viruses

A

Parvovirus

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14
Q

Group 3

A
  • (+/-) dsRNA
  • Viral dsRNA must be copied to make dsRNA for new virus particle (requires RNA-dependent RNA Polymerase)
  • vRdRp copies dsRNA genome and also transcribes vmRNA
  • vmRNA translated to viral protein.
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15
Q

Genome replication of reoviruses and birnaviruses

A
  • Both have segmented genomes
  • Genome replication is monocistronic (each gene encodes a single mRNA and a single protein)
  • Replication occurs within the capsid in the cytoplasm, not in the nucleus as for DNA viruses
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16
Q

Example of Group 3 viruses

A

Rotavirus

17
Q

Group 4

A
  • (+) ssRNA
  • Viral (+) RNA can act as mRNA and directly accessed by cellular ribosomes to translate viral protein
  • Viral RdRp copies (+) strand to (-) complementary RNA
  • (-) RNA used as template for synthesis (by viral RdRp) of (+) ssRNA for incorporation in new virus particle
18
Q

Examples of group 4 viruses

A
  • SARS-CoV-2
  • Dengue virus
  • Sindbis virus
  • Poliovirus
19
Q

Group 5

A
  • (-)ssRNA
  • (-) RNA cannot be accessed by cellular ribosomes. (+) copies ie. viral mRNA must be made first
  • Viral mRNA is synthesized from (-) RNA template by vRdRp that is packaged into the virus and is ready to be used upon infection
  • (-) RNA template is also used to synthesise (+)
    vRNA intermediate which serves as the template for (-) vRNA for packaging into new virus particle
20
Q

Example of group 5 viruses

A
  • Influenza virus
  • Measles virus
21
Q

Group 6

A
  • (+) ssRNA (RT)
  • Retroviruses convert diploid (+) RNA genome to cDNA (RdDp) with the viral reverse transcriptase, that is packaged into the virion.
  • (-) ssDNA acts as template for synthesis of dsDNA intermediate.
  • This dsDNA is integrated into host cell chromosome with viral integrase.
  • When cells are activated, viral mRNA is transcribed with cellular DdRp, then translated to viral protein.
  • Packages as diploid genome (2 copies of ss(+)RNA per virion)
22
Q

Group 6 example virus

A

HIV

23
Q

Group 7

A
  • (+/-) dsDNA (RT)
  • dsDNA viruses with a gapped genome, with an RNA intermediate
  • Immediately upon infection of cell, DNA gap is repaired by cellular DdDp (a covalently closed circular form of vDNA is synthesized: cccDNA)
  • cccDNA is template for transcription of
    viral mRNA and subgenomic/pregenomic RNA
  • Serves as template for the viral reverse transcriptase (RdDp) , for production of viral DNA genome
24
Q

Example of group 7 virus

A

Hepatitis B virus

25
Q

DNA directed DNA polymerases proofreading

A
  • Proofreading capabilities in the form of exonuclease activities
  • Most RNA-dependent RNA polymerases do not possess this capability (causes higher error)
  • Many of these errors cause lethal amino acid changes, while other mutations may appear in the genomes of infectious virus particles
26
Q

RNA viruses’ RNA-dependent RNA polymerase fidelity

A

Differs in how accurately they copy viral genomic RNA

27
Q

Enzyme that provides proofreading function in RNA viruses

A

ExoN, a 3’ - 5’ exonuclease

28
Q

Viral quasispecies

A
  • RNA polymerases lack 3’ exonuclease proofreading activity
  • Mutations accumulate during replication and recombination
  • RT lack 3’ exonuclease activity and retroviruses mutate and evolve at rates similar to those of non RT RNA viruses
  • Retroviruses also exist as quasispecies
29
Q

Average error frequency of RNA polymerases

A

1 in 10^4 - 10^5

30
Q

Most mutations are inconsequential or result in viruses which are not able to replicate. How can some mutations benefit viruses

A

By enabling viruses to:
- Successfully evade the immune system
- Develop drug resistance
- Thwart vaccination strategies

31
Q

What does process of recombination that occurs in RNA viruses lead to

A

The formation of chimeric molecules
from parental genomes of mixed origin

32
Q

Co infection of a cell by genetically distinct viral strains

A
  • Leads to the generation of recombinant viruses.
  • Can occur in both non-segmented viruses or within a segment of a segmented virus.
33
Q

Co-infection of a cell by genetically distinct strains of a retrovirus

A

Leads to the generation of ‘heterozygous’ virus particles, after which a template-switching event can
lead to a recombinant provirus.

34
Q

Retroviral genome

A

Psuedodiploid (2 RNA strands)

35
Q

Why are retroviruses considered not truly diploid

A

Because only one allele at each locus is preserved in the integrated provirus, and any progeny produced from a cell harboring a single recombinant provirus will transmit only one allele at each locus in its progeny.

36
Q

Reassortants

A
  • If a cell is infected with two different influenza viruses, the RNAs of both viruses are copied in the nucleus
  • When new virus particles are assembled at the plasma membrane, each of the 8 RNA segments may originate from either infecting virus.
  • The progeny that inherit RNAs from both parents are called reassortants.
37
Q

Pandemic IVA

A
  • Express HA that has not been seen by most people before (there is no pre-existing immunity to that new virus)
  • This HA may have originated in a pig (swine) or bird (avian)
38
Q

HA

A
  • Hemagglutinin
  • The molecule that attaches to the receptor and against which the protective immune response is targeted
39
Q

Viral diversification mechanisms

A

Recombination and reassortment

MICR3320 (14 decks)

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