How HIV Affects and Its Treatment using Combination Therapy

Question

Can someone please help me with the following questions. I've written my specific questions right after the text question.

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Human immunodeficiency virus (HIV) is a retrovirus. Its genome is a single (+) stranded RNA that is packaged with the reverse transcriptase enzyme within a protein capsid. This is further packaged into an envelope that is derived from the plasma membrane of the host cell in which the virus had replicated. The surface of the envelope is covered with the envelope glycoprotein, called gp120 & gp41.

a) HIV specifically infects the T-helper (TH) cells of the human immune system. If the HIV enters the host cell by means of host receptor recognizing a viral protein, what would be the most likely ligand and its corresponding receptor during HIV infection?

b) Some individuals are resistant to HIV infection even after repeated exposure. Assuming that these individuals express a normal level of the functional receptor that you have recognized above, how can you explain their resistance to HIV?

c) In recent years, therapies have been developed to fight AIDS using nucleotide analogs. The drug used to combat AIDS is Azidothymine (AZT). The structure of AZT is very similar to thymidine except that in AZT, the 3’-OH group on the deoxyribose sugar is replaced by an azido (N3) group. Which process of the life cycle of HIV do you think is inhibited by AZT?

d) Combination therapy is the new treatment strategy for treating HIV patients.

i. Why is combination therapy more successful in preventing the emergence of the disease resistant clones?

ii. If the combination therapy involves a drug that prevents…

1) HIV binding to the target cell, what protein does this target?

2) Integration of HIV genome into host cell genome, what protein does this target?

3) The cleaving of viral polypeptide into individual proteins, what protein does this target?

e) If the AIDS patient were given combination therapy, would the patient still be able to transmit the HIV virus to his/ her partner (Yes/ No)? Explain your choice.

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a) No idea.

b) Maybe their T-helper cells have some sort of mutation that makes it impossible for HIV to bind to them?

c) I'm thinking "formation of HIV RNA" because in the absence of 3' -OH bonds, phosphodiester bonds cannot form.

d) i. It kind of makes sense because a virus being resistant to multiple drugs would be very unlikely but maybe there's some definite reason why?

ii. No clue. Is this talking about proteins of the virus or of the host? Also, enzymes are also proteins, right?

Answer 1

a) HIV uses a certain receptor that's expressed widely on T helper cells. As this is homework I suggest looking at the wikipedia article to look this up for yourself. It is under tropism.

b) You mentioned mutation. That's very true but this question is excluding people with that mutation called the delta 32 mutation. Thus HIV can infect these people, but what happens to any virus in the context of infection? How does the human body deal with viral infections. Is there any variation that would account for why some people can be resistant to HIV and others not be?

c) Yes! Well done :) You're thinking along the right lines. Look up the drug on wikipedia and look up it's mechanism.

d) i) Yeah exactly that. But more than that. There's optimal HIV which in the absence of drugs does the best job at infecting. If we give a drug then HIV has to mutate away from optimal HIV to stay alive, but it's weaker. Give multiple drugs and it can't mutate away from all of them because if it did it would be so far from optimal it would be a rubbish virus.

ii) 1) It could affect the HIV binding receptor protein or the protein with which it binds on the host cell. So both! Logic would dictate we would use self receptor blockade because at least they're more conserved but I'm sure both are probably used. Enzymes and receptors are both proteins.

2 + 3) Look up the lifecycle of HIV

e) Theoretically possible. He might not take the drugs. If he takes the drugs unlikely because the virus basically becomes undetectable. Look this up, it should be on wikipedia again.