11 - RNA Viruses Flashcards
Big difference between DNA and RNA viruses
RNA viruses and more likely to evolve/mutate faster than DNA viruses due to absence of proof reading mechanism
Influenza virus
- Single strand (-) sense RNA
- RNA is segmented
- Each segment codes for one or two proteins
- Envelope glycoproteins HA
and NA critical for entry and
exit of virus into host cell
Influenza A
- All IVA are viruses of birds
- 18 HA and 11 NA identified
to date
what does the H and N stand for in H1N1
Hemagglutinin and Neuraminidase
Genetic reassortment
- ‘Mixing’ of RNA via coinfection of a host cell by more than one IV
- Can result in formation of IV with genomes which have never been seen by human immune systems
- infection can result in very severe disease and high rates of death
Infuenza antigenic changes
Structure of hemagglutinin (H) and neuraminidase (N) periodically change
Influenza antigenic changes (shift)
- Major change, new subtype
- Exchange of gene segment (reassortment): resulting virus is immunologically distinct from previous IV
- no existing immunity
- May result in pandemic
Influenza antigenic changes (drift)
- Minor change, same subtype
- Point mutations in HA and/or NA genes: pre- existing immune response cannot control replication
- May result in epidemic
Coronaviruses
(+) sense, enveloped, non segmented RNA viruses with largest genomes of RNA viruses: ~30 kb
Human immunodeficiency virus
- Family Retroviridae
- Icosahedral, enveloped ss(+)RNA
- Infects CD4+ cells by binding of viral gp120
- Quasispecies
- CD4+ T cell count gradually and consistently declines
How does HIV replicate
By conversion of viral RNA to complementary DNA (viral reverse transcriptase), which then integrates (viral integrase) into host cell genome (provirus), remains integrated for life of cell
Quasispecies
a group of related variant viruses that arise by mutation
HIV-1
Cause of almost all human infections. May have come from chimpanzees
HIV-2
A less aggressive disease progression. Genetically more closely related to simian immunodeficiency virus (SIV)
Group M HIV-1
Dominant form worldwide. Clades A-K within group M
Circulating recombinant forms (CRF)
Emerging variants of HIV-1 that are combined clades
HIV transmission
- Injecting drug
- Transfusion
- Contaminated equipment
- During delivery
- Breast milk
- Sexual
Early phase HIV infection
- Initial viruses are macrophage tropic
- Envelope glycoprotein gp120 is able to bind to CD4 molecules and chemokine receptors called CCR5
- Relatively ‘non virulent’
Late phase HIV infection
- Viruses are T cell trophic, having gp120 capable of binding to CD4 and CXCR4 found on T4 lymphocytes
- Highly virulent
- Induces syncytia
What is the appearance of T tropic HIV viruses associated with
Rapidly declining CD4 counts and AIDS
Diagnosis of AIDS
CD4+ T cells <200 cells/μl
Conclusion of the Sydney Blood Bank Cohert (Long Term Non Progressers)
Attenuation of the HIV-1 genome, specifically the nef gene, interferes with viral replication and can influence disease outcome
CCR5-delta32
Slow progressers that were homozygous for a 32bp deletion in the CCR5 gene (results in a frame shift and generates non functional receptor for HIV-1)
CCR5
Chemokine receptor expressed on T cells, macrophages, dendritic cells and microglia