Human immunodeficiency virus HIV Flashcards
in the scope of understanding viral infections.
what is the clinical hall mark of HIV
reduced CD4 below …
in 1981 what were the two main diseases observed in a cluster in certain groups of people that lead to the discovery of AIDs
– pneumonia caused by a yeast, Pneumocystis carinii,
– and an unusual tumour called Kaposi’s sarcoma caused by human herpes virus 8
AIDS was first identified in what groups of high risk individuals
homosexual men, intravenous drug users and haemophiliacs.
what was the unusual aspect of the cluster of diseases observed in 1981
they were only seen in immunosuppressed people not in those with fully functional immune systems
when was the virus that causes Acquired immunodeficiency syndrome first isolated
• 1983 - isolated from lymph node of an infected individual by Luc Montagnier’s group in Paris and was called the human immunodeficiency virus, or HIV for short
when was the second strain of HIV identified
1986
how do the two strains HIV-1 and HIV-2 differ
in their virulence and geographical location.
HIV-2 is less virulent than HIV-1 and is found primarily in western Africa.
what primate species do HIV-1 and HIV-2 come from
HIV-1 came from chimpanzees and HIV-2 from the sooty mangabey.
HIV-1 and HIV-2 are both natural viruses of what and how did they initially infect humans
natural viruses of primates
animals are killed for food and assumed that it was during this process that the virus initially infected humans.
what is the major difference between the HIV-1&2 infectivity in primates vs humans
HIV-1 and HIV-2 do not cause immunosuppression in chimpanzees or sooty mangabeys - only when the virus crossed species to humans does it cause profound immunosuppression
how many people were infected with HIV in 2020
1.5 million
where is the highest rate of increase in HIV infections
sub-Saharan Africa; estimated 20-40% of young adults are infected. (life expectancy now halved to 30-40)
what is the difference in the spread of HIV between genders in africa compared to europe, usa and oceania
in africa it has similar incidence between men and women
in europe and oceania it is much more prevalent in men than women - used to be the same for the usa but the pattern is changing with more women being infected
at the end of 2008, women accounted for ___ of all adults living with HIV worldwide
50%
what family of viruses is HIV a part of
Lentivirus family
what type of virus is HIV
a retrovirus
what is the genome of HIV like
HIV genome contains 2 molecules of single-stranded RNA, each bound by a molecule of reverse transcriptase. (RNA->DNA)
what two major HIV elements are in its genome
p10 protease and a p32 integrase.
what is the HIV genome surround by
a nucleocapsid consisting of inner layer of protein p24 and outer layer of protein p17 (both part of Gag (group specific antigen) polyprotein complex)
what is the outer portion of the virus made from
Consists of lipid envelope derived from host cell membrane
Contains two viral proteins, gp120 and gp41,
(viral envelope proteins)
what does the gag-group specific antigen gene code for in HIV
encodes core viral structural capsid proteins: p24, (a nucleoid shell protein); several internal proteins, p7, p15, p17 and p55
what does env envelope gene of HIV encode
the viral envelope glycoproteins gp120 and gp41
what does the pol polymerase gene encode in HIV
the viral enzymes, protease (p10), reverse transcriptase (p66/55; alpha and beta subunits) and integrase (p32).
what are the three largest genes in the HIV-1 genome
gag (2000bp), pol (2900bp) and env (1800bp)
how does membrane associated Gag trigger budding of virion from surface of cell
attracts two copies of viral RNA along with cellular and viral proteins that trigger budding of virion from surface of cell.
what viral protein of HIV facilitates binding to the CD4 on the host cell
gp120 envelope protein
what cells does HIV infect
glycoprotein-CD4+ cells (T cells, monocytes, dendritic cells)
what cells express CD4
CD4 T cells, monocytes and dendritic
what is CD4
is a co-receptor assisting T cell receptor (TCR) in communicating with an antigen-presenting cell (APC) by binding to MHC in the non-polymorphic region
describe the normal function of CD4
During antigen presentation, TCR complex and CD4 recruited to bind to different regions of the MHCII molecule (α1/β1 and β2, respectively).
Close proximity between the TCR complex and CD4 means Lck kinase bound to the CD4 cytoplasmic tail is able to phosphorylate tyrosine on the Immunoreceptor tyrosine activation motifs (ITAM) present on the cytoplasmic domains of CD3.
Phosphorylated ITAM motifs on CD3 recruits and activates SH2 domain-containing protein tyrosine kinases (PTK) e.g. Zap70 to further mediate downstream signal transduction via tyrosine phosphorylation, leads to transcription factor activation including NF-κB and consequent T cell activation
describe the steps of the HIV lifecycle
1) . Binds to CD4 +ve cells through gp120 to CD4; interactions between virus and chemokine co-receptors.
2) . Nucleocapsid enters the cell, unfolds, releasing viral RNA, which is reverse-transcribed to DS DNA.
3) . The viral DNA integrates in the host genome, where it lies dormant as a provirus.
4) . Following cell activation, viral DNA directs the transcription of viral RNA.
5) . Viral proteins are translated from the RNA.
6) Viral proteins and single-stranded viral RNA assemble to form new viral particles.
7) . Virus buds from the cell, picking up some of cell membrane, complete viral particles can infect other cells. Takes the host cell membrane as its envelope
how does HIV circumvent normal dendritic cells to increase t cell interaction for infection spread
An HIV-infected dendritic cell shoots out thin projections called filopodia with virus particles at their ends. Actin filament rearrangement projects filopodia in a waving arc towards T-cells at μm/sec, facilitating 800 dendritic cell - T-cells interactions/hour
describe the new model of HIV binding
- gp120 binds onto host cell surface to the receptor CD4. Causes a conformational or structural change of gp120, which in turn, allows gp120 to bind again, this time to a chemokine coreceptor, usually CXCR4 or CCR5.
- Once bound, gp41 is released from its high energy state and the previously buried fusion peptide springs out towards the host cell membrane, bridging the divide between the virion and the host cell membrane
what is the relationship between gp160, gp120 and gp41
gp160 is sparsely distributed on the virus envelope and is displayed as trimers. Each gp160 is comprised of an external component gp120 and gp41,
gp41 is a transmembrane protein that binds to and anchors gp120.
what are M tropic variants (now called R5 viruses)
variants that use the beta-chemokine receptor CCR5 for entry and are thus able to replicate in macrophages and CD4+ T-cells.
(CCR5 present on CD4 t cells, monocytes and dendritic cells)
what are T trophic variants (now called X4 viruses)
use the alpha-chemokine receptor, CXCR4, for entry. only infect t cells.
how can HIV entry be inhibited (chemokine receptors)
by downregulation of the expression of the coreceptors or by saturating them with their ligands
what is the normal structure and function of chemokine receptors
G-protein-coupled with seven membrane-spanning domains
normally function by binding to chemokines in order to direct leukocytes to migrate to sites of inflammation.
what natural mutations can effectively protect people against HIV
A nonfunctional mutant allele of CCR5 with an internal deletion of 32 bp (CCR5Δ32) is found with high frequency in European and North American populations, and this effectively protects individuals against M-tropic virions
what mutation may affect the co receptor binding and disease progression of HIV
A guanine to adenine point mutation (3′UTR801G/A) in stromal-cell-derived factor 1 (SDF-1), a ligand for CXCR4, has been reported in 40% of healthy Asian Indians.
Insertions in the promoter region of macrophage inflammatory protein 1α (MIP-1α), a ligand for CCR5, have been reported in 1 in 5 Indians
which protein mediates fusion between the viral envelope and host cell membrane for entry of HIV
gp41
