HIV Flashcards
What Kind of virus is HIV
An enveloped ribonucleic acid (RNA) retrovirus
What happens after exposure to HIV?
HIV virus is transported via dendritic cells to the lymph nodes where the infection becomes established.
Followed by viaemia and dissemination to lymphoid organs which are main sites of viral replication
What is the main site of HIV replication
Lymphoid organs
Describe a mature HIV viron
Mature viron’s have a lipid membrane lined by a matrix of protein studded with glycoproteins 120 and glycoprotein 41 spikes.
The inner cone shaped protein core (P24) houses x2 copies of the single stranded RNA genome and viral enzymes
What are the 3 characteristics retroviral genes in HIV?
gag = encodes a polyprotein that is processed into structural proteins
pol = codes for enzymes : reverse transcriptase,integrase and protease
env = codes for envelope proteins GP120 and GP41
What cells does HIV infect? and where?
Cells with the CD4 receptor e.g. T-helper cells; lymphocytes; monocyte-macrophages; dendritic cells and microglial cells in the CNS
HOw does HIV enter cells?
By binding of gp120 to the CD4 receptor - results in conformational changes in gp120 that permits binding to 1 of 2 chemokine co-receptors (CXCR4 or CCR5)
What is CCR5 used for
utilised during initial infection but later virus may adapt to use CXCR4
How are people immune to HIV
They are homozygous for the CCR5 delt-32 muitation and so don’t express CCR5 on their CD4 cells. (v rare)
What happens after chemokine receptor binding?
a membrane fusion and cellular entry involving gp41.
After penetrating the cell and uncoating the DNA a copy is transcribed from the RNA genome by the reverse transcriptase enzyme that is carried by the infecting viron.
Then the viral DNA is transported to the nucleus and integrated withyin the host cell genome by integrase enzyme
What is HIV integrated virus? and what happens next
Proviral DNA and persists for the life of the cell.
Cells infected with pro-viral HIV DNA produce new virons only if they undergo cellular activation resulting in the transcription of viral mRNA copies which get translated into viral peptide chains.
What role do polyprecursor polyproteins play in HIV viraemia?
They are clevaed by the viral protease enzyme
Forming new viral structured proteins and enzymes
(these migrate to the cell surface and are assembled using the host’s cellular apparatus to produce infectious viral particles - they bud from the cell surface and incorporating the host cell’s membrane to form a viral envelope.)
What is CD4 lymphocyte replicating HIV life cycle length? and how do they die
Short. ~1 day. killed by host immune system response
How are sanctuary sites formed for HIV virons in the body?
Small amounts of T-helper lymphocytes go into post-integration latent phase
Describe the 2 types of host immune response to HIV infection
Humoral = development of antibodies to a wide range of antigens.
Cellular = dramatic expansion of HIV-specific CD8 cytotoxic T-lymphocytes - CD8 lymphocytosis and reversal of the usual CD4;CD8 ratio leading to CD8 cytotoxic T-lymphocytes killing activated CD4 cells that are replicating HIV (except latently infected CD4 cells)
HIV evades destruction despite big immune response because of the highly conserved regions of gp120 and gp41 that are necessary for viral and attachment to cells and are covered in highly variabl.e glycoprotein loops that change over time because of mutations selected for by the immune response.
