RNA viruses Flashcards
Factors that decide a virus’s tissue tropism
1) Cell receptors
2) Proper expression of transcription factors and replication co-factors that recognize viral promoters and enchancer sequences
3) Ability of cells to support viral protein synthesis
4) Presence or absence of physical barriers, including pH, temp, O2 tension…
Sequence of Viral Spread
1) Implantation at portal of entry
2) Local replication and local spread
3) Dissemination from portal of entry
4) Multiplication in target organ
5) Shedding of virus
At what point in viral spread do you usually see clinical disease?
multiplication in the target organ
What is incubation period?
Time between exposure to the virus and onset of disease: extends from implantation until virus replicates in target organ causing symptoms
What is pathogenesis?
Process by which an infection leads to disease. Results from viral disruption of normal cellular processes.
Name basic pathogenesis for following viruses:
HIV
Hep C
Poliovirus
HIV: immunosuppression and syncytia formation
Hep C: liver dysfunction, primarily as a response to host defenses
Poliovirus: Host “shut-off” phenomenon
-also applies to vesicular stomatitis virus, encephalomyocarditis, influenza
What is host shut-off phenomenon
Some viruses induce a shutoff of all host cellular protein synthesis with a shift to viral protein synthesis.
Severe stress for cell:culminates in lysis and tissue destruction
ex: rhinovirus, polio, influenza
Positives and negatives of viral induced apoptosis (with nuclear inclusions)
Positive: small scale apoptosis blocks viral replication and spread
Negative: Systemic apoptosis leads to massive tissue destruction with sever pathogenesis
Processes of viral infection that trigger disease, with examples
1) Toxic effects of viral gene products on cell metabolism (host shutoff)
2) Host response to infected cells (liver damage from Hep C, syncytia formation from HIV)
3) Modification of cellular function due to interaction of cellular genes and proteins with viral products (oncogenic viruses)
4) Lytic destruction of host cells (acute viral infections)
What is the difference between mutation and recombination?
Mutation: error is incorporated into the viral genome
Recombination: coinfecting viruses exchange genetic information creating novel virus
What is mutation rate for DNA viruses?
Approximates rate for eukaryotic cells: 10^-11 errors per nucleotide per round of replication
Due to proofreading polymerases
Only one mutant per several hundres-thousands of genome copies
What is antigenic drift?
mutations that produce viruses with new antigenic determinants that can cause disease in previously resistant host
AKA quasispeciation
What is the key criteria for viral recombination?
Co-infection of a single cell with two or more viruses. Can be different strains or different types of virus.
What are the 3 types of Viral Recombination?
Independent reassortment
Homologous recombination
Breakage/re-joining
Key features of independent reassortment
Viruses must have segmented genomes
Process involves genes residing in different pieces of nucleic acid being randomly assorted
Results in generation of a virus with new antigenic determinants and new host ranges: Antigenic shift –> major cause of epidemics such as 1918 influenza
Key features of homologous recombination
Occurs by template switching during RNA replication
- Must have homology for direction switching
- Common in RNA viruses and retroviruses
- requires NO breaks!
ex: multi-drug resistant HIV
Every HIV genome produced is likely a product of ~8 of these “template switching” recombinations
Key features of breakage/re-joining
Requires nucleic acid break or fragmentation
Fragments are ligated: only viruses still able to replicate survive
Co-infecting viruses must have similar genomes
Prevalent among DNA viruses; occurs in large RNA viruses
ex: generation of SARS coronavirus
Major Bio features of Orthomyxoviruses
Prototype: Influenza
Enveloped, segmented, negative-stranded (remember: influenza is non-sense!)
Lipid bilayer with hemagglutinin and neuraminidase spikes
Carries RNA-dependent RNA polymerase
Type specificity common internal antigens NP and M1
Subtype specificity envelope antigens hemagglutinin (HA) and neuraminidase (NA)
2 mechanisms by which influenza alters its antigenic constitution
By altering antigenic constitution, influenza delays clearance by the immune system
Antigenic Drift: gradual accumulation of minor mutation –> seasonal flu differences
Antigenic Shift: sudden, major change in the antigenicity of a virus due to recombination of the virus genome with another genome of a different antigenic type
-immune system fails to recognize new antigenic type –>epidemic and pandemic strains
Transcapsidation:
lab technique where cell is infected with 2 different viruses and the genome of one is inserted into protein structure of another
ex: generation of viral vectors for gene therapy
Main features of HCV virus
Flavivirus: + ssRNA; enveloped
Main features of SARS
Coronavirus: +ssRNA; enveloped
Major features of influenza
Orthomyxovirus
Carries out independent reassortment: ex 2009 H1N1 had 4 distinct recombination events
Enveloped, segmented, negative-stranded
Lipid bilayer with hemagglutinin and neuraminidase spikes
Carries RNA-dependent RNA polymerase
Type specificity common internal antigens NP and M1
Subtype specificity envelope antigens hemagglutinin (HA) and neuraminidase (NA)
Course of infection:
inhaled
proliferate in epithelial cells of upper respiratory tract
disseminates to target: lower respiratory tract
What is viremia?
Virus in the blood (Spread through the circulation). Virus enters organs from capillaries by multiplying in endothelial cells or fixed macrophages, diffusing through gaps, carried by migrating leukocytes.
Basis for many diagnostic tests
4 Major methods of viral dissemination
1) Viremia
2) Nerve cells (rabies)
3) Cell trafficking
4) Direct cell-to-cell (syncytia - HIV)
Distinct histological feature of cells infected with CMV
Cells devotes lots of energy to making dark, black inclusion bodies –> eventual apoptosis
4 Mechanisms of Viral Diversity
1) Mutation
2) Recombination/reassortment
3) Replication rate/number of progeny (polio: 1 - 10,000 virions in a single day)
4) Selective Pressure
What is an escape variant?
Viral strain that has acquired mutations that allow it to evade immune responses or resist certain drugs
Problematic for antiviral and vaccine development
Best method for battling extreme viral diversity and resistance due to rapid mutation
ex- HIV: Mutants resistant to every combination of drug (current and future) arise thousands of times everyday,
just by chance
Treat with drug cocktails, never miss doses, keep developing new drugs
Major Features of Hepatitis C virus
Flaviviridae family: + ssRNA ; enveloped
Causes chronic infection in 80% of people
Major cause of liver damage world wide (200 M infected)
Error prone replication, so many quasispecies variants –> limitation to antiviral therapy, immune function and vaccine strategies
What does recombination do that point mutations do not?
1) Juxtapose combinations of mutations that would have a low probability of occurring all at once (multi-drug resistance)
2) Juxtapose viral genomes with limited homology (intertypic recombination) (attenuated polio virus regaining virulence from enterovirus in Guatemala)
3) Transduce sequences from nonhomologous genomes (low frequency) (recombine with host genes: can be oncogenic!)
What is an emerging virus?
A newly discovered virus or a virus that is increasing/has the potential to increase in incidence
What are the major contributors to viral emergence?
High mutation rates
Recombination
Human-made changes to environment: dams, air travel, xenotransplant, urbanization, daycares…
Key features of West Nile Virus
Flavivirus (same family as Hep C): + ssRNA ; enveloped
80% of infections are asymptomatic
Picornaviruses
+ssRNA; non-enveloped
polio
Hepatitis A
Reovirus
medium-sized, nonenveloped, icosahedryl
linear dsRNA, segmented
Readily reassorted
ex: rotavirus: kills 1M children in developing countries each year
Key features of Paramyxoviruses and examples
ssRNA, negative sense; enveloped; NON-segmented
Measles
Mumps
parainfluenza
Respiratory syncytial virus (RSV)
3 determinants of viral pathogenesis.
- Accessibility of virus to the tissue.
- Virus susceptibility to host defenses.
- Cell permissiveness to viral multiplication.
