03/09a RNA Viruses I Flashcards
What are the three major clinically important families of (+) RNA viruses?
Flaviviridae
Picornaviridae
Togaviridae
What are the major clinically relevant members of Flaviviridae?
Tropical fevers - yellow fever, dengue fever, West Nile virus
Hepatitis C
What are the major clinically relevant members of Picornaviridae?
Poliovirus
Rhinovirus
Foot and mouth disease
Hepatitis A
What are the major clinically relevant members of Togaviridae?
Chikungunya
Equine Encephalitis viruses
Rubella
Where does the life cycle of the (+) strand RNA virus take place?
ENTIRELY in the cytoplasm
Do (+) strand RNA viruses need a 5` cap and a polyA tail?
NO - they can use unconventional translation templates since their genomes double as mRNA
Poliovirus has no 5 cap and a virus-encoded polyA tail
Hepatitis C has no 5 cap and no polyA tail
Rotavirus and yellow fever have a host-provided 5` cap
What is the significance of rotavirus NS3 protein?
Provides a bridge between the viral mRNA and the host cell translation machinery (eIF4G specifically), allowing translation of viral proteins to occur
Replaces the polyA binding protein (rotavirus doesn’t have a polyA tail)
Also inhibits host protein synthesis, since host mRNA can’t bind to eIF4G if NS3 is bound
Allows to virus to make lots of protein very quickly, and interrupts host cell defense mechanisms
Why is poliovirus unsuitable for efficient ribosome scanning? List five reasons
1) No 5 cap
2) Long 5 UTR
3) Extensive stable secondary structure
4) Cryptic start codons
5) Numerous stop codons in every reading frame
How does poliovirus carry out protein translation?
Ribosomes are recruited internally, without the need for the 5` cap
Initial translation results in proteases that cleave the normal host cell translation complex
End result - viral proteins are being efficiently produced, while host protein translation is inhibited
What is the major salient feature of (+) strand RNA virus replication?
Extremely high error rate of the viral polymerase
What is a ‘pseudospecies’ virus?
A species of virus that has such a large degree of genomic variability (due to the high error rate during replication) that it has no clearly defined genomic sequence
What are the advantages and disadvantages of being a pseudospecies virus?
Advantages - genetic adaptability allows for development of resistance, high processivity of replication machinery, efficient life cycle (fast!)
Disadvantages - error catastrophe leading to loss of viability, forced genetic austerity results in only a small amount of proteins being made, simple life cycle limits plasticity
How have (+) strand RNA viruses adapted to the high error rates in their replication?
By limiting the size of their genomes - monocistronic genomes (polyproteins are later processed) and multifunctional gene products
Recombination promiscuity
Genetic complementation
High processivity
What is the price of limiting the size of the (+) strand RNA viral genome?
NO complex regulation of gene regulation - all or nothing translation, no regulatory regions, no latency
NO modulation of genome replication - all or nothing
Genetic austerity - limited array of gene products and functions
What is template switch?
A method of recombination in (+) strand RNA viruses
During RNA genome replication, the replication machinery switches between templates
This can allow the replication machinery to avoid possible errors and increase the likelihood of producing viable progeny
