Viral pathogens - classification, biology and diseases Flashcards
What are the different structures of viral genomes?
What is the generic central dogma?
How do viruses use the central dogma?
How are virsues classifed?
Describe the structure of HIV
Describe a mature HIV-1 particle
= circulating in blood looking for cells to infect
How is the genome of HIV organised?
Describe what a envelope protein consists of
What does a virus require to enter the cell?
- engagement of the viral envelope proteins with cellular receptors so the virus is able to attach and fuse into the cell cytoplasm
Describe the process of HIV-1 enters the cell
What is the relevance of a cell needing to express CD4 for HIV-1?
**If the cell does not express CD4 - the virus cannot get into the cell
**If the cell does not express CD4 and the co-receptor then the envelope protein cannot function
HIV is therefore attracted to CD4 expressing cells eg. helper T cells and macrophages - resulting in immunodeficiency and AIDS
What happens after the HIVirus has entered the cell?
After the virus has entered the cell, it has to move to a site of replication (area in which the replication of the genome is most favoured for HIV)
- Within the cell nucleus
- But the distance between the cell membrane and nuclear membrane is large so…
HIV utilises the cellular microtubules network to move the core containing the genome to the nuclear membrane by the viral genome RNA having a number of capsid modifications
How does HIV convert it’s RNA to DNA?
Via Reverse transcription
- The reverse transcription enzyme in the mature HIV-1 particle mediates this
- RNA genome is bound by an RNA primer and the reverse transcriptase enzyme acts as a polymerase making new copies of RNA from the template. The RNA template is then transferred to DNA template and becomes double stranded which is then inserted into the viral genome and that the cellular gene.
How does the Virus integrate its DNA into the cellular DNA?
via Retroviral integration using the viral integrase enzyme
How does retroviral integration work?
- enyzme makes a cut whilst bending the linear viral DNA around the cellular DNA
- viral integrase enzyme binds both host and viral DNA
What is the role of LEDGF and TRN-SR2?
= pre-integration complex which reocnisges the cellular DNA and guides the viral DNA to it
How does the virus get the required proteins for mRNA transcription?
The virus recruits to the viral genome cellular proteins required for mRNA transcription
- Enhancer region
- Promotor region
The HIV-1 promotor region contains bindings sites for transcription factors that are present in T-lymphocytes
- Transcription factors promote and enhance transcription from the viral genome in the cellular genome
How is it that the virus ensures that it’s RNA are given preferential treatment and preferential production of RNA?
Viral Tat protein gets produced from transcription = viral RNA binding protein and will specifically bind to viral RNA and enhance production of RNA
- Positive feedback mechanism - and allows for preferential treatment over cellular DNA.
What is the process of splicing in Retrovirus RNA?
What does the HIV-1 REV protein do?
= mediates nuclear export of unspliced and singly spliced viral RNA
How are new viruses made from viral proteins?
The unspliced HIV-1 RNA is the mRNA for Gag and Gag-Pol proteins:
- Dimerization of unspliced viral RNA allows packing of 2 genomes
- Gag and Gag-Pol proteins assemble viral particles
What new cells does HIV want to infect?
T-cells as they have CD4 molecule on their cell membrane which is required for virus entry
How does replication of virus within T-cells leads to killing of T-cells?
As you get more HIV, you get more T-cell killing
Viral load set point = minimum number of HIV particles you can have without the immune system detecting it
During clinical latency, number of T cells gradually falls and falls (with no symptoms)
Symptoms only present 6-8 years since virus has been present –> drop in T cell numbers, which stimulates more HIV copies to be replicated and appearance of opportunistic infections
Death is at the point opportunistic infections overwhelm the individual resulting in death
Why is immunodeficiency advantagous to the virus?
- To evade the normal type of immune response, some viruses replicate in the immune cells whose function is to recognise and kill infected cells
- This hides the virus from immune cells and inhibits immune cell function
- Inhibition of immune cell function allows other pathogens to replicate in virus infected hosts thus disease occurs
