L20 Flashcards
explain HIV
- human immunodeficiency virus
- retrovirus family
-targets T helper cells on human cells - HIV genome consists of 2 identical single stranded, positive sense RNA molecules, also encodes structural + non-structral proteins
acute vs chronic HIV infection vs AIDS
acute
- develops within 2-4 weeks after infection
- flu like symptoms
- HIV multiples rapidly, enters CD4 lymphocytes, spreads in body
- level of HIV in blood very high, increases risk of transmission
chronic
- HIV continues to multiple, but at lower levels
- may not show HIV related symptoms
- without ART (antiretroviral therapy) , advances to AIDS in 10years
AIDS
- final, severe stage
- HIV damages immune system, so allows opportunistic infections
- diagnosed if have a CD4 count of less than 200cells/mm3 (HIV cells out number CD4 cells) or have a certain opportunistic infection
- high viral load able to transmit HIV to others easily
-without treatment, 3 yrs survival max.
steps of replication of HIV
- binding: HIV attacks a CD4 cell, binds to receptors on surface using viral surface molecules
- fusion: after HIV attaches, HIV viral envelope fuses with CD4 cell membrane, allows HIV to enter cell, then virus releases HIV RNA + HIV enzymes (e.g. reverse transcriptase, integrase, protease)
- reverse transcription: HIV releases + uses reverse transcriptase to convert its RNA into DNA, this conversion allows HIV to enter CD4 cell nucleus + combine with cells genetic material
- integration: once inside CD4 nucleus, HIV releases integrase, inserts its viral DNA into genome of host cell, when CD4 cell replicates, the HIV provirus is passed form 1 cell generation to the next, ensuring ongoing replication of HIV
- replication: once HIV integrated into host CD4 cell DNA, virus begins to use its machinery to create long chains of HIV proteins, act as the building bocks for more HIV particles
- assembly: new HIV RNA + HIV proteins made by CD4 cell, move to surface of cell + assemble into immature non infectious HIV
- budding: immature HIV pushes itself out of CD4 cell, once outside, new HIV uses protease to break up the long protein chains into immature viruses, that then create mature (infectious) virus
how to block HIV at reverse transcription step + at penetration
- non nucleoside reverse transcriptase inhibitors (NNRTI), binds + blocks HIV reverse transcriptase (prevents conversion of HIV RNA into HIV DNA)
- prevents HIV from replicating
- but RNA polymerase does not have ability to check nucleotides during transcription, or proofread, but the NRA can cope with the errors
- over time, slightly different versions of HIV particles build up over time (quasispecies)
fusion: CCRS (receptor) agonists
explain antiretroviral therapy (ART)
- HIV requires a COMBINATION of HIV drugs to treat
- 3 antiretroviral drugs, from atleast 2 different HIV drug classes
- the drugs prevent HIV from multipling,r educes the amount fo HIV (viral load) in body
- less HIV in body = chance for immune system to recover + produce more CD4 cells to fight/ reduce risk of HIV transmission
- act by blocking attachment + entry, inhibiting fusion, inhibiting reverse transcriptase, inhbiiting integrase, inhibiting protease
explain influenza virus
- enveloped virus, negative sense RNA segmented genome
- encodes 11 viral genes
-virus has evolved lots of mechanisms that allow it to invade/take over host cell machinery
explain genetic reassortment
- process by which influenza viruses swap gene segments, occurs when 2 differing influenza viruses co-infect a cell
process of antigenic drift
- allows for accumulation of mutations + genetic ressortment (a disease affecting ducks, but not humans, may pass onto pigs, mutates, and then can affect humans)
- each yr, flu vaccine contains 3 flu strains (2 A strains + 1 B strain)
- after vaccination, body produces infection fighting antibodies against the 3 flu strains in the vaccine
- if exposed, antibodies latch onto virus’s HA antigens, preventing the flue virus from attaching to healthy cells + infecting them
- influenza virus genes, made of RNA, more prone to mutations the genes made of DNA
- if HA gene changes, so can the antigen that it encodes, causing it to change shape
- if HA antigen changes shape, antibodies that normally would match up no longer can, allowing newly mutated virus to infect body’s cell
- called antigenic drift
how do NA inhibitors block the release of influenza virus
- as particles are budding from the cell, NA cleaves the sialic acid residues from the cell surface, so virus be released
- cells stuck to cell surface, as sialic acid hasn’t been removed
blocks the release of influenza cell
