HIV - virology & immnology Flashcards
6 steps of HIV virology
- attachment
- cell entry
- interaction with host cells
- replication
- assembly
- release
describe attachment
viral and cell receptors
describe cell entry
only central viral ‘core’ carrying the nucleic acid and some associated proteins enter host cell
describe interactions with host cells
use cell materials (enzymes, amino acids, nucleotides) for their replication; subvert host cell defence mechanisms
describe replication
may localise in nucleus or in cytoplasm or in both
production of progeny viral nucleic acid and proteins
describe assembly
occurs in nucleus, in cytoplasm or at cell membrane
describe release
by bursting open of cell;
or by exocytosis from the cell over a period of time
9 steps of replication of HIV
- Attachment
- Entry
- Uncoating
- Reverse transcription
- Genome integration
- Transcription of viral RNA
- Splicing of mRNA and translation into proteins
- Assembly of new virions
- Budding
what does HIV infect
HIV infects cells that express CD4 and the interaction between cd4 AND GP120 is conserved among all primate lentiviruses
what does binding of gp120 to CD4 induce
a conformational change in gp120
what does the co receptor binding site include
a conserved bridging sheet and also amino acids in the V3 loop
describe immune response to HIV
Vigorous immune response but no demonstrable protective immunity with rare exceptions
Excessive immune activation which favours viral replication
Immunological dysfunction with involvement of all elements of host defence
Ongoing viral replication with progressive immunological impairment leading to clinical manifestations of immunodeficiency
what is HIV-1
retrovirus that evolved from a simian immunodeficiency virus in chimpanzees
It replicates in CD4 positive cell
The virus copies its RNA into DNA and used the host cell for gene transcription
what does HIV-1 result in
gradual damage to the immune system mainly through depletion of CD4 T-cells
what kind of virus is HIV
A retrovirus - an RNA virus which uses reverse transcriptase to make a dna copy that becomes integrated into the DNA of the infected cell
HIV genome structure
small rna virus - expresses just 10 genes
member of retrovirus family - uses reverse transcriptase to make DNA copy of itself
lentivirus - characterised by long incubation period
how does HIV interact with CD4 receptor
HIV fuses to cd4 receptor and passes its contents into the CD4+ cell
what are co receptors for HIV
CCR5 and CXCR4 chemokines receptors
when is CCR5 used
used by HIV-1 in early infection byt may switch to use CXCR4 later in infection
once viral integration has occurred, infection persists for life in a reservoir of latently infected cells
what are targets for antiretroviral therapy
integrate inhibitors
fusion/entry inhibitors
reverse transcriptase inhibitors
proteases inhibitors
describe genetic resistance to hIV
1% of caucasians are homozygous for a 32bp deletion in the CCR5 gene - this is necessary for primary HIV1 ifnection
people wit only one copy of the mutant gene can be infected with HIV but show delayed disease progression
why does HIV evolve rapidly
due to
- error prone replication (the enzyme reverse transcriptase makes at least 1 error in every replication cycle)
- rapid viral replication (generation time - 2.5 days)
-large population sizes
what increases hIV-1 diversity
recombination between different classes/subtypes in the same person
describe acute hIV-1 infection
detectedion of v high levels of virus in blood
symptoms of acute retro viral fever
what are the symptoms of acute retro viral syndrome
glandular fever
fever
sore throat
oral ulcers
skin rash
neurological features
what do immune responses during AHI (acute HIV0 determine
long term viral control
disease progression
why is early invitation of acute hiv 1 ifnection beneficial
reduced risk of transmission
smaller reservoir
lower set point
delayed progression
clinical features of untreated HIV-1
- vaginal/ oral candidiasis
- skin disease
- fatigue
- bacterial pneumonia
- herpes zoster
- oral hairy leuopkplakia
- thrush
- fever
- diarrhoea
- weight loss
why does the immune response to hiv 1 not clear the virus
antibodies develop against most viral proteins, byt neutralising antibodies take months to develop and rarely neutralise the primary hiv strains that are transmitted from person to person
the response of CD4+ T helper cells is lost early on because HIV infects them first
there is a v vigorous response from cytotoxic CD8+ T cells which provides the major force controlling viral replication but fails when immune exhaustion sets in
