How Viruses Replicate Flashcards
Why are viruses not good targets for antivirals?
because viruses use many host cellular products for replication and we can’t target at own’s cell machinery
What is HIV primary and secondary receptors?
primary: CD4
secondary: CCR5 and CXCR4
What is influenza’s primary receptor?
sialic acid
What does tropism determine?
what kind of cell the virus can infect and species of animal the virus can infect (zoonotic transmission)
- if a cell does not have the viral receptor, the virus can NOT infect the cell
- sometimes, viruses can enter certain cells, but if cell is missing a cellular factor required for viral replication, virus won’t replicate
T/F: If primary and secondary receptors, only one has to be present
False!
Both must be present to infect cell
What are the 2 modes of entry for viruses?
- enveloped viruses can fuse the lipid bilayer of virus with cell membrane (some naked viruses can make a hole in cell membrane for entry)
- both enveloped and naked can be endocytosed. lower pH of endosome helps virus enter cytoplasm from endosome by causing conformational change of some viral proteins
What is uncoating?
release of genetic material from the virus
Where does most virus replication take place? What are the exceptions?
- mostly: nucleus
- exceptions:
poxvirus- cytoplasm
HBV- both nucleus and cytoplasm
What is the virus replication process of herpesvirus?
1) DNA into nucleus
2) Host RNA polymerase II transcribes early gene transcription factors
3) Second wave gene: transcription factors and viral DNA polymerase
4) Viral DNA replication
5) Late gene production- structural proteins made
6) Viral assembly in nucleus/progeny virus
What DNA viruses have no viral DNA polymerase?
- papillomavirus
- polyomavirus
- parvovirus
- requires the cell to be in S phase of cell cycle for virus to replicate
What viruses can cause cell-cycle deregulation by inhibiting pRb and making the cell go into cycle?
- papillomavirus
- polyomavirus
most of the time, this isn’t a problem but if the cell isn’t killed it can become cancerous (commonly seen in papillomavirus- HPV 16&18)
What virus cannot cause the cell to enter the S-phase and must infect cells already replicating?
- Parvovirus
replicates in erythrocyte progenitor cells and can cause anemia
How do papillomavirus, polyomavirus, and parvovirus replicate without viral DNA polymerase?
1) DNA into nucleus
2) Host RNA polymerase II transcribes early gene transcription factors
3) Need an actively dividing cell to replicate their viral DNA
4) Viral DNA replication
5) Late gene production- structural proteins made
6) Viral assembly /progeny virus
What viruses use their own viral polymerases to make more genetic material?
- Adeno
- Herpes
- Pox
- Hepadna
Which DNA virus replicates in the cytoplasm?
poxviruses
- have a viral DNA-dependent RNA polymerase used to make messenger RNA
Which DNA virus replicates in both nucleus and cytoplasm?
hepadnavirus (HBV)
- has reverse transcriptase which is important for antiviral therapy for HBV infection targets the HBV reverse transcriptase
What is mRNA the same as?
+ssRNA
What are the steps of RNA virus replication?
- +ssRNA virus enters cells and right away makes protein making a large polyprotein (exception retroviruses)
- cleave polyprotein to make individual viral protein via viral protease
- make a viral RNA-dependent RNA polymerase that was cleaved out of polyprotein
What does +ssRNA viruses have that make them great targets for antiviral drugs?
- viral polymerase (made from cleavage of polyprotein)
- viral protease
What are retroviruses?
- +ssRNA viruses have 2 copies of same genetic material
- unique because make a DNA copy of themselves by using reverse transcriptase as part of replication cycle
How do retroviruses make the polyprotein?
- retroviruses use cellular RNA polymerase to make viral messenger RNA from the integrated viral DNA
- this viral mRNA travels to cytoplasm to get made into protein
- the polyprotein is cleaved by a viral protease which helps mature the viral particle
What takes reverse transcriptase into the cell in retroviruses?
virion
- only they make a DNA copy of their genetic material, they integrate that copy into host cell chromosome and the viral DNA copy is in the cell for the rest of the cell’s life
In -ssRNA viruses, what is the first thing they do when they enter the cell?
make mRNA from their -ssRNA using viral polymerase that they carried with them in their virion
- SO, they do NOT need a viral protease because they make mRNA for each viral protein
- DO require viral polymerase
What is characteristic of -ssRNA viruses?
all helical and enveloped
(all other RNA viruses are icosahedral)
How do -ssRNA viruses make mRNA?
- use their -ssRNA
- viral polymerase is carried into the cell in their virion
- do NOT require viral protease
Why is Hepatitis D virus (-ssRNA) defective?
HBV is required for HDV to replicate
What RNA virus makes a polyprotein when it enters the cell?
+ssRNA
What is antigenic drift?
- small changes
- mutation
- happens with every virus
What is antigenic shift?
- large changes
- gene recombination/reassortment
- seen in pandemics
Which are the exceptions for virion assembly in the nucleus of DNA viruses?
- poxvirus
- hepadnavirus
What is required in genetic recombination?
- requires 2 very similar viruses to infect the same cell
- results in several proteins being replaced at a time between strains resulting in a large change
What is required in genetic reassortment?
- segmented genome
- ex: BOAR viruses
Order the mutation rate from lowest to highest in regards to antigenic drift:
higher eukaryotes (lowest) < prokaryotes < DNA viruses < RNA viruses (highest)
Why are RNA viruses more likely to have a higher mutation rate?
because most RNA viruses cannot proofread (a base inserted by mistake will not be corrected)
What is a viral quasi species?
- bunch of similar but not identical viruses in a host due to high mutation rate during replication
- especially seen in RNA viruses (HIV)
T/F: Most mutations in viruses are helpful for virus and can spread in population
False!
Most will actually harm the virus and not be passed onto when a new person is infected/
viruses that are infective for a long time like HIV are more prone to mutation and be beneficial to the virus and can spread through a population
Why do antiviral therapies sometimes not work (especially in HIV)?
- it’s possible that when an antiviral therapy is started, a virus was carrying a mutation that was resistant to the antiviral
- this is why combination therapy (2-3 different classes of drugs) is necessary in HIV and HVC
