L15 - Virus Lifecycle: Replication And Protein Expression Flashcards
List 8 types of virus genomes
DsDNA, ssDNA, ssRNA, dsRNA, circular, linear, non-segmented, segmented
What are the 4 diff polymerase and what do they do
DNA dependent DNA polymerase (DNA from DNA)
DNA dependent RNA polymerase (RNa from DNA)
RNA dependent RNA polymerase (RNA from RNA)
RNA dependent DNA polymerase (DNA from RNA, reverse transcriptidase)
Where does DNA virus get DNA polymerase? How can virus make RNA from RNA
DNA virus - more complex virus can encode for their own DNA polymerase, others use their host polymerase
RNA virus - RNA from RNA: no such enzyme in eukaryotes → virus produced enzyme
All RNA viruses encode an RNA dependent RNA polymerase. How does it differ in +ve strand vs -ve strand
+ve - genomic RNA acts as mRNA to produce more RNAs it doesn’t need to carry the polymerase
-ve strand - needs to carry polymerase bc it needs to be converted to +ve after entry
What is the significance of polyprotein in poliovirus? As a way to make protin using RNA
Viral RNA acts like mRNA.
• 5’ end has VPg instead of a cap, helping ribosome recognition.
• Uses an Internal Ribosomal Entry Site (IRES) for ribosome binding and scanning.
• Translation starts at the start codon to produce a single large polyprotein.
• The polyprotein is not functional as-is.
• Viral proteases cleave it into multiple functional proteins needed for the virus.
How does coronavirus use its +ve sense RNA genome for replication and protein production?
Has a +ve sense RNA genome (longer than most RNA viruses).
• RNA acts like mRNA for translation.
• Gene 1 (RNA polymerase) is translated first after entry.
• RNA polymerase copies full-length +ve RNA to –ve sense template, then back to multiple +ve sense RNAs.
• Translates at multiple start points, producing different mRNAs.
• Each mRNA leads to production of specific proteins needed by the virus.
How does influenza virus express proteins from its segmented RNA genome?
• Has a segmented genome (8 RNA segments).
• Each segment encodes one protein via mRNA transcription.
• Segments 7 and 8 produce two proteins each using alternative splicing (a eukaryotic mechanism).
• To use splicing, influenza replicates in the nucleus of host cells—unusual for RNA viruses.
How do new strains arise through genome re-assortment?
Mixing of diff genomic segments produce novel strain of influenza virus (genetic shift - reassortment of genomic segments creates poly novel strain of influenza virus)
How do retroviruses use the host cell machinery to express their genes?
• Retroviruses integrate their genome into the host DNA as a provirus.
• Host cell transcribes the provirus like its own genes.
• Produces one primary transcript that encodes the entire genome (e.g., envelope proteins, reverse transcriptase).
• Uses host splicing machinery.
• Alternative splicing creates multiple different mRNAs, each encoding a specific viral protein.
What is the targets of antiviral drugs
Attachment antagonists,, inhibit uncoating, inhibit DNA/RNA synthesis, blocks maturation
What are some therapeutic targets that aims at HIV life cycle
- smaller molecules inhibits entry
- antibodies prevent binding to structures
- prevent reverse transcription (blocking the enzyme)
- viral integrase (blocking to prevent provirus)
- viral protease is used for alternative splicing so blocking this prevents making other genes
What are some problems with therapeutic drugs?
- however, the virus can mutate so the therapeutic wont work anymore
- so you use more than one drug at the same time for optimal efficacy (lots of targets = less likely to mutate to be consistent to all the targets)
- stop taking drugs = virus can come back
Influenza drug targets
- inhibits process of fusion and uncoating of virus ( blocks acidification and conformatinal change to gain entry)
- inhibiters of RNA polymerase
- haemagglutin binds to sialic acid, when it exits it is still able to bind to surface. so for the virus to be released, we need another enzyme called neuromonidase.
- it chops off receptors allowing virus to be released
- inhibitors of this enzymes prevents the virus from spreading to other cells
SARs CoV 2 drug targets
- block entry using antibodies
- expression of viral genes: large protein processed using proteases, this is blocked to prevent production of RNA polymerase
- small molecules prevent replication
- drugs block the consequences and dampen the immune response and symptoms but not the actual viral particle
