HIV Flashcards

Question

Describe the genetic diversity of HIV.

Answer 1

Mutates at the highest rate of any known biological entity due to reverse transcriptase. Lots of viral genetic diversity in the HIV of a singular patient- evades the immune system/ drugs very quickly if not kept under control. HIV DNA mutations more likely in genetic hotspots containing homopolymeric nucleotide runs (repetitions of the same base.?)

Answer 2

RT: Turns RNA genome to DNA genome. No proof-reading in RT - no function to detect mutations allowing mutations to occur in resulting DNA.

Answer 3

Approx 3.4x10^-5 number of mutations per site occurs within each replication cycle . Human rate: roughly 2.5 x10^-8 per base per generation

Answer 4

It has many things ( RT, intergrate protease..) that humans do not have in their body. This makes them easy to target without causing 'off-target effects' on mitrochondira, cells ect.

Answer 5

ENTRY Inhibitors - stop HIV attaching to the host cell fusion inhibitors- stop HIV from fusing and uncoating RT inhibitors - NRTIS/ NNRTIs Intergrate inhibitors - Stops HIV integration to the host genome Protease inhibitors - stop HIV building its protease maturation inhibitors

Answer 6

NRTI drugs - Nucleoside reverse transcriptase inhibitors Get incorporated into the DNA during reverse transcription and terminate the chain - Lack a 3’-hydroxyl group Can have severe side effects - Interfere with mitochondrial DNA synthesis Mutations in RT can reduce the enzymes affinity for the drug or allow for excision of incorporated drug

Answer 7

NNRTI - Non-nucleoside reverse transcriptase inhibtiors. Also interfere with RT but bind to the enzyme instead of interfering with the DNA. Stop protein domain movement – RT Enzyme can no longer bind DNA Very few side effects - RT homologues not found in humans. Resistance also occurs through mutations in RT - Change/block drug binding pocket

Answer 8

Blocks integrase activity: Stops genome integration into host genome by Binding directly to the enzyme in multiple places. Used often to salvage patients who have RT mutations: can’t take NRTIs or NNRTIs. Well tolerated. Resistance mostly due to mutations in the integrase gene: Binding pocket of the drug in the pre-integration complex (Nucleoprotein complex consisting of viral and human proteins). Can also occur from mutations in the nef gene

Answer 9

Protease inhibitors. Block cleavage of gag and pol precursors (Often analogues of the cleavage site) , stopping protease activity, creating a defective viral particle. Associated with lipid accumulation around neck/back. Mutations in protease (cuts up large HIV precursor proteins into smaller proteins which combine with HIVs genetic material to form new HIV virus) seem to enlarge the substrate binding pocket, creating resistance. Mutations in gag (structural protein of HIV-1/retroviruses) can also cause resistance

Answer 10

Entry Inhibitors: 3 forms: Block CD4 binding (gp120). Block fusion (gp41). Block chemokine (coreceptor) binding (gp120). co-receptor inhibitors - bind to the host protein and compete with the virion. Generally low adverse effects. Resistance occurs through mutations in gp120 or gp41 - not as recurrent/predictable as other resistance patterns, appearing to be protein structure modification rather than specific mutations.

Answer 11

Block CD4 binding (gp120) Block fusion (gp41) Block chemokine (coreceptor) binding (gp120)

Answer 12

Post-exposure prophylaxis, anti-retroviral drug. Used when HIV is caught soon after exposure to be cleared from the body. Uncertainty about how to carry out this treatment - 2/3 drugs seem to be effective within a week of exposure. Treatment given for 4 weeks. Regular 6-12 weekly follow-ups undertaken to check for infection.

Answer 13

Preventative treatments. Anti-retroviral drugs for high-risk groups. Stops HIV from taking hold in recipient. >99% effective. Must be coupled with safe sex training and regular testing.

Answer 14

Truvada: Tenovir and Emtricitabine (NRTIs) in combination

Answer 15

Most vaccines work by eliciting a small set of neutralising antibodies against a few viral surface proteins

Answer 16

HIV has a very high mutation rate Viral virions can remain dormant so its hard to target all of them Difficult to elicit a strong antibody response without being already infected.

Answer 17

Most trialled vaccines shown to be ineffective, however: Broadly neutralising antibody VRC01 has been found to be effective against 90% of circulating strains: Binds the CD4 contact site of gp120. Only produced years post-HIV infection- Vaccine would need to elicit the production of these antibodies pre-infection NCT05001373: mRNA-based vaccine trial. Engineered HIV envelope proteins to elicit germline B-cell responses. Only began in October 2021

HIV Flashcards

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