Section 6.2 Flashcards
2) Parvoviruses: (genome)
linear ssDNA
*smallest animal DNA viruses
3) circoviruses:
Circular ssDNA
* similar to geminiviruses that infect plants
4) papillomaviruses:
Circular dsDNA
*examples: HPV: warts, infection can lead to cervical cancer
5) polyomaviruses:
circular dsDNA
*example SV40
6) Adenoviruses
All the following viruses reply on:
Cellular RNA and DNA polymerase machinery for replication/transcription
Parvoviruses replicate in _____
cells with activated cell cycles (cuz they can’t activate a cell on their own)
parvoviruses clinically:
B19 infection: erythema infectiosum “fifth disease”
parvoviruses genomic content
very simple 2 genes
1 gene encoding non-structural proteins that interact with things inside the cell for the virus to replicate (generated by diff RNA splicing)
1 gene coding structural (capsid) protiens
parvovirus structure:
(capsid and what’s inside it)
small naked icosahedral capsid (very stable)
- inside capsid: linear ssDNA folded in the ends into T structures that allow initiation of DNA replication
Parvoviruses can only infect cells in the __-________ that are actively replicating their DNA
(cuz its viral genomic DNA can’t act as a template for transcription and they need host cell DNA to replicate)
S-phase
parvoviruses are now used as potential
oncolytic viruses; kill cancer cells
gene therapy vectors: AAV deliver genes
parvoviruses diversity fun facts: (3)
- high mutation rates*
*Make lots of ERRORS (rdrp don’t proof read) - also very frequently engaged in recombination when more than one strain co infects a host
- most of its diversity are viruses that don’t infect humans
Veterinary parvoviruses: (2)
feline panleukopenia parovirus (FPV)
canine provirus (CPV)
feline panleukopenia parovirus (FPV)
known to infect cats, replicates in bone marrow and lymph nodes (leukopenia) and intestine (causing hemorrhagic enteritis)
canine provirus (CPV)
identified in dogs and rapidly spread around the globe (high mortality similar to FPV)
CPV has been characterized and found to originate from a cross species transmission of FPV to dogs
original CPV only infects dogs
now dominant CPV infects both dogs and cats
What led FPV to become CPV
two substitutions in the capsid proteins allowed for transmission to dogs
several other mutations allowed infection of both dogs and cats
ANOTHER veterinary parvovirus
Aleutian mink disease virus (AMDV)
Aleutian mink disease virus (AMDV)
global spread
problem where
replicates where
facts (transmission and stability)
how is it lethal
globally distributed due to transport of infected animals before recognition as infectious disease
is a major problem for farms
replicates in macrophages causes chronic infection (never cleared)
highly transmissible spreads quickly
very stable in environment (super compact virions)
virus antibody complexes block arteries and deposit in tissue therefore lethal
intersting about the evolution of AMDV
the two genes (structural and non structural) were evolving differently and at diff rates
(sturctural ones were evolving slower than non structural ones)
Normal evolution
structure (capsid) protiens evolve quick due to immune pressure
non-structural don’t evolve, are under strong selection to maintain function in host cell
Therefore AMDV displays:
antibody dependant enhancement (antibodies stimulate infection, help the virus get taken up by host cell)
Therefore, vaccine makes it worse and second infection is worse cuz u have antibodies
selection acts to maintain immune epitopes
Polyomaviruses: (genome and structure)
circular dsDNA wrapped In histones making nucleosomes (mini chromosomes) packaged inside capsid
Polyomavirus infection effects:
widespread in humans but usually doesn’t cause overt symptoms and presists as long term infection
Only causes skin cancer in immunocompromised
Polyomavirus example:
SV4 = simian virus 40
SV40 accidentally spread how?
contaminant in polio vaccine ( was in the mockey cell culture used and was not innactivated in the process of inactivating polio)
productive infection of SV40 causes:
Non-productive infection of SV40 causes:
productive: cell lysis and virion release
non-productive: happens in non-permissive cells where the genome doesn’t replicate and no virions form
(can transform cultured cells into tumour cells)
- but, the virus protiens that are called t-antigens that expressed and stimulate cell division and lead to cellular transformation (if it integrates to genome, continus T-Ag expression
Cellular transformation by SV40
(in susceptible but non permissive cell)
- genome goes inside and makes T-Ag
small T-Ag activates the MAPK pathway
medium T-Ag activates cell cycle through Src pathway
Large T-Ag interacts with diff cellular protiens p53 and rb that effect cell cycle
Adenoviruses structure:
icosohedral structure with fibre projections at 12 vertices that interact w cell receptors
Adenovirus genome:
linear dsDNA (similar to phage)
— has terminal repeats
—- has a protein attached to 5’ end of ds molecules (so 2 in total)
Very Important for DNA replication
Adenoviruses led to discovery and noble prize win of ______
RNA splicing
same region makes many diff RNAs and protiens
Adenoviruses and “the end problem”:
all linear DNA genomes have end problem cuz they need a primer to initiate replication on lagging strand
- to prevent loss of DNA bits each replication
how do parvoviruses linear dsDNA get rid of “the end problem”
folds itself to make DNA hairpins
how do herpesviruses linear dsDNA get rid of “the end problem”
circularize their genome and do RCR
how do Adenoviruses linear dsDNA get rid of “the end problem”
4 STEPS
use a special protein (terminal protein: TP) that acts as primer for DNA replication (recruits DNA pol) at inverted terminal repeats
1- Starts as Pre-TP that brings viral DNA pol to terminus of the DNA genome and a C base attaches to it where DNA synthesis begins
2- the displaced strand is covered with a viral DNA binding protein DBP
3-after completion we have a full DNA duplex and pTP gets cut by a protease to become TP
4- displaced strand reaneals using the repeated inverted sequences
5- this process repeats (2 full dsDNA genomes after each replication)