Viral pathogens - classification, biology and diseases

Question 1

What are the different structures of viral genomes?

Answer 1

Question 2

What is the generic central dogma?

Answer 2

Question 3

How do viruses use the central dogma?

Answer 3

Question 4

How are virsues classifed?

Answer 4

Question 5

Describe the structure of HIV

Answer 5

Question 6

Describe a mature HIV-1 particle

Answer 6

= circulating in blood looking for cells to infect

Question 7

How is the genome of HIV organised?

Answer 7

Question 8

Describe what a envelope protein consists of

Answer 8

Question 9

What does a virus require to enter the cell?

Answer 9

• engagement of the viral envelope proteins with cellular receptors so the virus is able to attach and fuse into the cell cytoplasm

Question 10

Describe the process of HIV-1 enters the cell

Answer 10

Question 11

What is the relevance of a cell needing to express CD4 for HIV-1?

Answer 11

**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

Question 12

What happens after the HIVirus has entered the cell?

Answer 12

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

Question 13

How does HIV convert it’s RNA to DNA?

Answer 13

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.

Question 14

How does the Virus integrate its DNA into the cellular DNA?

Answer 14

via Retroviral integration using the viral integrase enzyme

Question 15

How does retroviral integration work?

Answer 15

• enyzme makes a cut whilst bending the linear viral DNA around the cellular DNA
• viral integrase enzyme binds both host and viral DNA

Question 16

What is the role of LEDGF and TRN-SR2?

Answer 16

= pre-integration complex which reocnisges the cellular DNA and guides the viral DNA to it

Question 17

How does the virus get the required proteins for mRNA transcription?

Answer 17

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

Question 18

How is it that the virus ensures that it’s RNA are given preferential treatment and preferential production of RNA?

Answer 18

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.

Question 19

What is the process of splicing in Retrovirus RNA?

Answer 19

Question 20

What does the HIV-1 REV protein do?

Answer 20

= mediates nuclear export of unspliced and singly spliced viral RNA

Question 21

How are new viruses made from viral proteins?

Answer 21

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

Question 22

What new cells does HIV want to infect?

Answer 22

T-cells as they have CD4 molecule on their cell membrane which is required for virus entry

Question 23

How does replication of virus within T-cells leads to killing of T-cells?

Answer 23

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

Question 24

Why is immunodeficiency advantagous to the virus?

Answer 24

• 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

Question 25

What are the direct and indirect way HIV could promote T-cell killing?

Answer 25

Question 26

What is the difference between non-permissive and permissive CD4 T cells and how they are affected by HIV?

Answer 26

Question 27

What happens as a result of loss of T cells?

Answer 27

LOSS OF T CELLS –> IMMUNODEFICIENCY –> loss of immune system –> opportunity for opportunistic infections to colonise the HIV infected host

Question 28

What are HIV associated pathogens?

Answer 28

If you remove cells of the immune system, it means the immune system can no longer function

HIV infected individual can be colonised by any number of different pathogens = HIV associated pathogens:

• Viral (can cause death in HIV infected individuals) - see below
• Bacterial
• Fungal
• Parasitic

**HIV associated pathogens they can only infect humans who don’t have a functioning immune system**

Question 29

What are the 2 routes of infection in HIV positive individuals?

Answer 29

1. Primary infection

• Encounters virus for the first time and replicates
• Can be resolved

2. Reactivation from latency

• Depletion of T cells during HIV infection that allows that existing infection to reactivate from latency and cause disease
• Usually where the virus cannot access where the virus becomes latent

Question 30

What is a example of a opportunisitc infection from HIV associated viral pathogens

Answer 30

1. Herpes simplex virus (HSV)

• Virus gets in and replicates into the nerve cell or the dendrite whose processes are connected to the epithelial cell on left hand side and replicates
• Virus can move up and down axon from PNS or CNS
• Difference in movement is the difference between primary infection and latency - if it travels to one part eg. Dendrite and stays there = latency

Question 31

What is an opporuntistic infection?

Answer 31

= infections that occur more often or are more severe in people with weakened immune systems than in people with healthy immune systems.

For example:

Kaposi’s sarcoma herpesvirus (HSHV)

• Cancer of the skin caused by opportunistic infection and spreads very rapidly among all systemic organs

As well…

The link between cancer and HIV/Viruses is very strong - due to the loss of T cells and the results of opportunistic infection is cancer