How Viruses Replicate and Change Flashcards
T/F: Viruses use many host cellular products for replication; they are NOT good targets for antivirals
True
In regards to the attachment step in viral replication, viruses bind to…
cellular receptors on the host cell
In regards to the attachment step of replication, what is HIV’s primary receptor?
CD4
CCR5 or CXCR4 are secondary receptors
In regards to the attachment step of replication, what does Influenza use as its receptor?
Sialic acid
What cells have these viral receptors help determine….
the tropism of the virus or, put another way, what kind of cell the virus can infect
If a cell does not have the viral receptor….
the virus cannot infect the cell. Therefore, the viral receptor helps determine what cells the virus can infect or the tropism of the virus
There are other determinants of tropism other than receptors. Give an example:
Some viruses can enter certain cells, but if the cells are missing a cellular factor required for viral replication, the virus will not be able to replicate
T/F: Tropism determines what type of cell the virus infects but not the species of animal the virus can infect.
FALSE - tropism determines not only what cell type the virus infects but also the species of animal the virus can infect.
This becomes important in zoonotic transmission.
Entry at the cell membrane is mainly used for _______
enveloped viruses
Some enveloped viruses can fuse the lipid bilayer of the virus with the cell membrane. (Some naked viruses may make a hole in the cellular membrane for entry).
T/F: Both enveloped and naked viruses can be endocytosed
TRUE - The lower pH of the endosome helps the virus enter the cytoplasm from the endosome. (The lower pH causes a conformational change of some viral proteins allowing the virus to escape the endosome).
Where does most replication take place? What are some exceptions to this?
Nucleus
Exceptions:
-poxvirus –> cytoplasm
-HBV –> both nucleus and cytoplasm
Give an examples of herpesvirus replication
(immediate early)
1) DNA into the nucleus
2) Host RNA pol II
transcribes early genes-transcription factors
(Early - now can make copies of viral DNA)
3) Second wave genes-Transcription factors and viral DNA polymerase
4) Viral DNA replication
(Late - lots of structural protein made)
5) Late gene production-Structural proteins made
6) Viral assembly in the nucleus/progeny virus
Three DNA viruses do not make their own viral DNA polymerase; what are they?
Pappilomavirus
Polyomavirus
Parvovirus
What do papillomavirus, polyomavirus, and parvovirus use to replicate their viral DNA?
Cellular DNA polymerase
This means that the cells need to be in the S-phase of the cell cycle for the virus to replicate
Papillomavirus and polyomavirus can cause cell-cycle dysregulation by….
inhibiting pRb and making the cell go into cycle. Most of the time, this is not a problem as the cell dies. However, if the virus causes cell cycle dysregulation but does not kill the cell, there is a chance for the cell to become cancerous (hence cervical cancer with papillomavirus)
_______ cannot cause the cell to enter the S-phase and must infect cells already replicating
Parvovirus
Where do Poxviruses replicate?
In the cytoplasm, not the nucleus. They have a viral DNA-dependent RNA polymerase used to make messenger RNA
Hepadnavirus HBV has a reverse transcriptase. Why is this important?
Because antiviral therapy for HBV infection targets the HBV reverse transcriptase. HBV replicates in both the nucleus and cytoplasm.
Describe +ssRNA virus replication
1) The +ssRNA viruses can enter the cell and right away make protein. **Again, the first thing +ssRNA viruses do when they enter the cell is use the cell machinery to translate their +ssRNA into a large polyprotein (retroviruses are the exception)
2) They all need to cleave this polyprotein to make individual viral proteins. So, all +ssRNA viruses have a viral protease
3) They next need to make more RNA from their own RNA. The cell does not have any RNA-dependant RNA polymerase, so all RNA viruses need to make a viral RNA-dependant RNA polymerase (this protein is cleaved out of the viral polyprotein)
4) All +ssRNA viruses have a viral protease and a viral polymerase that are great targets for antiviral drugs
________ are +ssRNA viruses that have two copies of the same genetic material
Retroviruses
Why are retroviruses unique?
Because they make a DNA copy of themselves by using reverse transcriptase as part of their replication cycle. The reverse transcriptase is carries into the cell by the virus; it is in the virion
Describe the rest of the Retroviruses replication cycle after it makes a copy of it’s own DNA
1) One they make a DNA copy of their genetic material, they integrate that copy into the host cell chromosome. That viral DNA copy is in the cell for the life of the cell
2) Retroviruses next use the cellular RNA polymerase to make viral messenger RNA from the integrated viral DNA. This viral mRNA travels to the cytoplasm, where it gets made into protein
3) Retroviruses still make a polyprotein that needs to be cleaved by a viral protease. In HIV, the viral protease cleaves the viral proteins after the budding of the virion. The protease helps mature the viral particle.
Describe negative-sense RNA viruses replication (-ssRNA)
1) The most important thing to remember is that the first thing they do when they enter the cell is make mRNA from their -ssRNA. They do this using a viral polymerase that they carry into the cell with them in their virion
2) They do NOT need a viral protease because they make mRNA for each viral protein
3) They do require a viral polymerase that they bring into the cell in their virion
_______ viruses are all helical and enveloped
-ssRNA
__________ virus is a defective virus that MUST co-infect a cell with HBV to replicate
Hepatitis D
What are the two types of large changes seen with antigenic shift?
Gene recombination
Gene reassortment
What has to occur for gene recombination to take place?
For this to happen, two viruses of the same type infect the same cell. They might switch parts of their genome by recombination. This can result in several proteins being replaced at a time between the strains resulting in large change.
What do you need for gene rassortment?
Need a segmented genome. Viruses with a segmented genome have many pieces of genetic material, with each piece encoding one to two proteins. All of the separate sections of genetic material need to be packaged into each virus to be infectious.
Which viruses have a segmented genome?
BOAR virus families have segmented genomes
Bunyavirus
Orthomyxovirus
Arenavirus
Reovirus
When talking about gene reassortment, when does reassortment happen? What is reassortment responsible for?
-Reassortment happens when two strains of the same segmented virus infect the same cell. The resulting viruses have segments from both infecting strains resulting in a very different virus from the parental strains
-Gene reassortment is responsible for the majority of influenza pandemics
Different polymerases have different _______
fidelity; they have different error rates and ability to correct mistakes.
In regards to antigenic drift mutation, list the mutation rate in order of lowest mutation rate to highest mutation rate for different polymerases
higher eukaryotes < prokaryotes < DNA viruses < RNA viruses (highest mutation rate)
T/F: DNA viruses have higher mutation rates than RNA viruses
FALSE - DNA viruses have LOWER mutation rates than RNA viruses
Most RNA viruses cannot ______
proofread.
A base inserted by mistake will not be corrected, leading to a higher mutation rate
Describe viral Quasi-species
If you have a chronic infection, which allows the virus to replicate many times, you could have lots of different viruses in the body at ant one time (HIV and HCV) or put another way, many quasi-species of the virus.
-The ability of the virus to make single-nucleotide changes every 1-100 viruses made (depending on the virus) helps viruses to change rapidly with changing environmental conditions
-Most of these mutations will not be useful or will harm the virus and will not be passed on when a new person is infected
-(Remember, the virus that can replicate the best will be the predominant virus in the body. That is the virus that, more than likely, will be transmitted to a new person. Some viruses can withstand more changes than others or have a higher mutation rate. Therefore, these viruses will change more. All viruses will, however, acquire silent or conservative mutations over time. These mutations either do not alter the virus’s amino acids or make a
conservative amino acid change. So the sequence of the virus will subtly change over time with the accumulation of these mutations. Changes in the viral sequence are beneficial when tracking viruses in epidemiological studies of outbreaks.)
T/F: It is possible in chronic infections, when antiviral therapy is started, a virus carrying a mutation resistant to the antiviral is already present
TRUE - this can be true for HIV and HCV and why combination therapy is so necessary
