Lec 14-Genomes And Antiviral II Flashcards
(40 cards)
What does (+)-ssRNA virus genome do?
Mimics host mRNA and is directly translated into cytoplasm to make polyproteins. Viruses are always finding ways to mimic mRNA, just not always with a cap and poly-A tail
What do enveloped (+)-ssRNA viruses usually make? Where?
Make polyproteins at ER with many transmembrane domains
What do host and viral proteases do?
- Cut up long polyproteins into indiv proteins. Viral proteases typically cut themselves out
- Make RdRp’s
What do RdRp’s do?
Transcribe the gene to replicate it and make more RNA products such as (-)ssRNA intermediates and(+)ssRNA genomes. Viruses cannot have host enzymes do this, they have to make new genomes themselves
What does gene expression of (+)ssRNA on a zika virus translate?
The polyprotein translated is polymerase
What does (+)ssRNA make?
(-)ssRNA intermediate
What does (-)ssRNA intermediate make?
(+)ssRNA progeny genome
(+)ssRNA viruses will make ____ strands, used as template to make ___ strands
-, +
Polymerase reads ___ to make ___ or ___ to make ___
-, +, +, -
**will compliment any strand with its antiparallel strand
What is Ribavirin?
An antiviral drug
What are nucleoside analogs?
Many antiviral drugs are nucleoside analogs, meaning they resemble resemble a nucleoside
What virus does Ribavirin target?
Lots of them
Ribavirin is an inactive pro-drug. What does this mean?
Not activated until it is metabolized—is activated by phosphorylation
Incorporation of Ribavirin into RNA
Incorporated into RNA during genome replication:
- Ribavirin is chemically different enough that it loosens strict pairings of A-T and C-G
- Ribavirin is analogous enough to A and G both that it can bind to U or C
- Induces hypermutation in viruses that depend on RdRp
- This can be lethal to RNA viruses
Lethal hypermutation…what exactly happens?
Eg. (+)ssRNA original sequence
(-)ssRNA has R (ribavirin) replacing both A’s and G’s
(+)ssRNA doesnt know whether to bind C or U to R,
resulting in 2^n possible outcomes
How is hepatitis C transmitted?
Via blood
What does hepatitis C cause?
Hepatitis (liver disease) and liver cancer. People with chronic hepatitis C may need a liver transplant
Can hepatitis C be CURED?
Yes, with new anti-HCV drugs
How is HCV transmitted?
It is hard to transmit. Done through unprotected sex, blood/bodily fluid exposure, IV drug use
Can HCV be passed to animals?
No
What does Dr Lisa Barrett do?
Leads HCV elim in PEI and NS
What does Sofosbuvir do in HCV?
Sofosbuvir inhibits RdRp, resulting in no viral RNA synthesis. It is a prodrug for hep C, is metabolized into a nucleotide monophosphate to get phosphorylated and become an active triphosphate. This will be incorporated into the growing hep C molec, causing chain termination (stops the growing chain bc structure of ribose sugar in triphosphate inhibits elongation of new viral RNA)
Steps of coronavirus gene expression:
- Virus binds to host
- Attachment and endocytosis
- Release of viral genome into host cytoplasm. Has a (+)sense genome
- Engages with ribosome, starts making viral proteins through polyprotein synth
- Intermediate (-)sense genome is made
- Final (+)sense strand is made
What do polyproteins do in coronavirus gene expression?
Have 5’ cap. They dont go all the way to the end of the genome but they span most of it
