23-24: HIV Flashcards

Question

how do we ensure that the blood donor pool is HIV-free?

Answer 1

HIV incidence in first-time donors estimated at 2-3 cases/100,000 people annually use NAT where it can be detected sooner and is more sensitive - can always detect some viruses in the blood which are not latent sensitivity of tests matter - cannot detect HIV within the grace period so when there is infection, HIV can be replicating in just the tissue but not the blood - enough to cause infection but not enough to detect in the test

Answer 2

window period where very recent HIV infections cannot be detected for the most sensitive RNA assays, this can be between 10-16 days - infected people have contaminated blood but it won't be picked up by the test blood banks tend to screen people with high-risk habits (homosexual men - until 2015, homosexuals with at least one sexual encounter since 1997 forbidden from giving blood now, since 2020, homosexual men with at least one sexual encounter in the last 3 months cannot give blood

Answer 3

presents in primates which give rise to HIV in humans

Answer 4

syndrome it causes is unique

Answer 5

retroviruses have small RNA genomes use of an enzyme called reverse transcriptase to make a DNA copy of their RNA genome DNA copy of the viral genome can be inserted into the host DNA genome - can hide dormant or latent for years and be impossible to detect eventually, it will transcribe new copies of the viral DNA from the integrated DNA copy and assemble new infectious viral particles which contain an RNA genome to infect new cells - once in a while, reactivation and the cycle begins again

Answer 6

virion with two S-shaped molecules in the middle - RNA associated with viral proteins - identical genomes with reverse transcriptase envelope surrounding and protecting the virus - viral proteins inserted into the envelope - proteins responsible for reacting with receptors (similar to spike with COVID) envelope proteins called gp120 and gp41 - gp120 associated with attachment to receptors - gp41 associated in the fusion with a new cell immune system only sees/detects these proteins with an immune response and vaccination, you want to generate antibodies against gp120 since it is the only thing to detect the virus and prevent infection

Answer 7

gp120, gp41, protease, integrase, reverse transcriptase

Answer 8

carried in the viral particle in two copies - single strand of RNA of 9749 nucleotides and a few genes GAG, POL and ENV as key genes found in all retroviruses - find these in the human genome as well LTR encodes instructions for the expression and packaging of the genome ACC as additional accessory genes

Answer 9

GAG: - matrix protein - capsid protein - essentially forms the shell of the virus to protect the genome POL: - reverse transcriptase - protease - integrase - cuts strands into different pieces which become different proteins with different functions - forms enzymes and proteins ENV: - formation of gp120 and gp41 - long protein cut to form these proteins

Answer 10

lentiviruses have additional accessory factors while retroviruses all have GAG, POL and ENV proteins have specialised roles in the viral life cycle (immune evasion) - distinguish HIV from other retroviruses

Answer 11

part 1 gp120 attaches to CD4 receptors on T-cells - recognises CD4 molecule on the surface of T-cells - presence of CD4 required gp41 mediates membrane fusion, so viral capsid and RNA genome are delivered - changes structure and allows fusion of the cellular envelope of the virus with the cellular membrane of the host, realising the virus into the cytosome HIV can infect CD4 T-cells, macs and DCs (all important to immune response) since they all express CD4

Answer 12

CD4 is necessary but not sufficient to mediate viral entry second receptor called co-receptor required to permit viral entry - CCR5 or CXCR4 CCF5 and CXCR4 as chemokine receptors - normal function to detect chemokines (chemical signals) which tell immune cells where to go in the body gp120 binds to CD4, which brings it into contact with CCR5/CXCR4 - changes the structure of gp120 and then allows for exposure with gp41, then fusion

Answer 13

some individuals intrinsically resistant like prostitutes in africa who never got infected despite numerous exposure one group of resistant individuals found to harbour a genetic mutation in their CCR5 gene (32bp deletion) - rendered CCR5 non-functional and not expressed - virus can see CD4 but cannot find CCR5 to continue infection body can do without CCR5 and it is not essential

Answer 14

timothy ray brown developing leukaemia unrelated to HIV 10-15 years ago typically wipe out immune system and give them bone marrow cells, which will reconstitute and become the source of immune cells so development of a quasi-normal immune system with brown, infection with HIV so depletion of immune cells and replacement with bone marrow would mean that HIV still infects and kills all the new bone marrow cells so, they screened for blood donors with CCR5 genetic mutations and gave him that - bone marrow reconstituted immune system - now HIV-free

Answer 15

world's first genetically engineered babies where he took out CCR5 since people who are deficient can function normally but will be resistant to HIV

Answer 16

part 2 RNA genome reverse transcribed into a double-stranded DNA copy with reverse transcriptase DNA copy brought to the nucleus where integrase cuts the human genome at random, attaching the RNA genome to our own genome virus can be integrated and silent for a long time (latent) - virus therefore silences itself - never get rid of HIV

Answer 17

phenomenal mutation rates in reverse transcriptase as a polymerase for polymerase, 3 mutations per cell division typically in HIV reverse transcriptase, about 1 mutation every time it copies a genome - 10,000bp

Answer 18

low estimate of virion release into blood as 10B virions daily every virus slightly different from each other, with one or two point mutations on average, every possible mutation at every position in the HIV genome predicted to occur annually

Answer 19

infected with one HIV virus, but the whole population of viruses varies from each other by one or two point mutations

Answer 20

helps the virus evolve and evade antibodies immune system always playing catch up to eliminate the virus that already has an advantage hard to develop antivirals since the virus develops antiviral resistance - if we target reverse transcriptase, the drug will fit into a pocket and lock it from being functional/effective - mutations in the virus make the size of pockets different so the virus can escape and the drug doesn't fit only advantage is that viruses with mutations which may be resistant are typically not that good - virus forced to acquire many mutations, each of which is associated with a disadvantage for the virus

Answer 21

part 3 integrated provirus directs the creation of new RNA viral genomes with transcription, and new viral proteins with translation reactivation when viral RNA leaves the nucleus, using viral genomes, which are translated to make viral proteins protease cuts larger proteins into smaller proteins (reverse transcriptase, integrase, etc.) - powerful target for chemical drugs assembly of new viral particles and release

Answer 22

neutralising antibodies to prevent gp120 from binding to host cells - only viral protein exposed so targeted - gp120 however shielded by carbohydrates (sugars) so it is hard to detect - also that gp120 mutates which prevents recognition of the site by antibodies - virus can easily escape antibody responses CD8 T cells kill viral-infected cells - good CD8 T cell responses requires help from CD4 T cells which decline with AIDS - becomes less efficient as infection continues - CD8 T cells recognise peptides presented by MHC molecules but peptides also mutate while CD8 8 cells only recognise the exact copy of the peptide responses partially control but cannot eliminate HIV - replicates, mutates and outruns the immune system

Answer 23

not clear what kind of immunity to be elicited to provide protection - B cells and CTLs are good responses but what do we try to make more of? not clear on how to solve HIV mutability and variability - can generate a good response to wipe out the virus but always some mutated viruses that can take over the host again so you lose efficacy

Answer 24

highly active antiretroviral therapy (HAART) combination of multiple drugs to prevent emergence of drug-resistant variants - reverse transcriptase, protease, integrase and viral fusion inhibitors doesn't really help with emergence of variants since mutant viruses probably already exist but are relatively low and kept under control - statistically the viruses already exist drugs cannot cure HIV - latent in the DNA for the life of cells

Answer 25

reduces changes of getting HIV from sex by 99% and from injecting drug use (>74%) requires high levels of adherence, protects only against HIV and not other STDs pills taken daily that inhibit reverse transcriptase - descovy and truvada shots every two months as long-lasting integrate inhibitor - apretude

Answer 26

use of antiretroviral drugs (3 distinct drugs) after a single high-risk event to stop HIV seroconversion - during sex - sharing needles/syringes for drug infection - sexual assault has to be started as soon as possible to be effective - within 72 hours of possible exposure

23-24: HIV Flashcards

(51 cards)