HIV/AIDS Flashcards
single largest group who contracts HIV
men who have sex with men
how do you transmit HIV
exchange of infected bodily fluids that allows for entry of virus across a mucosal membrane or injected parenterally
blood, semen, vaginal fluid, breast milk
three routes of pediatric/perinatal HIV infections
transplacental
infected birth canal
ingestion of breast milk
how to decrease risk of infection from infected untreated mother?
treatment of both mother and infant with AZT or HAART (better)
structure of HIV
retrovirus related to lentiviruses
molecular structure of HIV
gag = core proteins pol = reverse transcriptase p24 = core protein; screening antibodies made to this gp120 = coat protein that binds CD4
HIV envelope expresses
the protein envelope that is capped by gp41 and 3 copies of gp120
lipids within the viral envelope are derived from
host cells on budding
HIV core includes
major capsid protein p24
nucleocapsid proteins
viral enzymes necessary for reproduction (protease, integrase, and reverse transcriptase)
two copies of genomic RNA
therapeutic protease inhibitors inhibit
cleavage of three large protein precursors that are coded for by the genome
What’s responsible for avoiding antibodies made against the virus?
genetic variability among the envelope glycoproteins
what does HIV have a tropism for
hematopoietic, nervous tissue
gp120 binds
CD4 molecule on lymphocytes, macrophages, dendritic and glial cells
fusion and entry into cells results from
interaction of gp120 with CCR5 or CXCR4 receptors
Describe what happens when the virus enters cell
virus uncoats
viral RNA and reverse transcriptase released
viral DNA synthesized
viral DNA integrated into host DNA (via integrase)
viral assembly and budding occurs on inner wall of host cell membrane
SEVI stands for
semen-derived enhancers of viral infection
Where is the HIV virus found in the body
within lymphocytes and monocytes, and in a cell-free state (in blood, fluids)
the increased presence of dendritic cells in the foreskin may in part explain
the increased transmission associated with uncircumcised males
what does virus require for entry into host cells
co-receptor CCR5 or CXCR4
virus infects cells that display
both CCR5 and CD4
some individuals who are apparently resistant to HIV infection have proven to be
homozygous for CCR5 mutations
how does a genetic change late in the infection alter the co-receptor
alter its co-recentpr requifrement from CCR5 to CXCR4
CCR5 is expressed on
monocytes and lymphocytes
monocytotropic (M-tropic)
CXCR4 (also known as fusin) is expressed on
only on T-lymphocytes
lymphotropic (L-tropic)
CXCR4 dependent virus causes
syncytia formation in lymphoid tissues
referred to as a syncytium-inducing strain of HIV
Switch to the CXCR4 phenotype is associated with
rapid loss of T lymphocytes and clinical deterioration
extremely poor prognostic sign
CXCR4 viruses bind to a wider range of T cell types, including naive T cell and thymocytes
switch allows viral destruction of more lymphocytes
CXCR4 switch is due to
hypervariable regions on the gp120 gene
inhibitions of viral replication may alter or delay this switch
activated CD8 cells produce
RANTES, MIP-1-a, MIP-1-b
bind to the CCR5 receptor and partially block virus uptake (inhibited once switched to CXCR4)
describe uptake of the virus
gp120 binds CD4 molecules - exposes new recognition sites for CCR5 or CXCR4
on binding of gp120 to co-receptor, gp41 binds
gp41 undergoes conformational change that results in the insertion of a fusion peptide that permits fusion of the virus membrane to the host cell membrane
plays an important role in establishment of the infection
infection of macrophages
macrophages provide
transportation of the virus throughout the body, including CNS
severe disease is associated with an
increase in virus proliferation and cytotoxicity in activated lymphocytes
primarily an infection of
lymphoid tissues
little presence of virus in peripheral lymphocytes
first phase decay due to
virus-specific CD8 T cell response
CD8 antiviral response destroys virally-infected cells and terminates early infection
second slower decay is thought to be due to
loss of longer lived viral reservoirs
progression of infection occurs because of three main factors:
- continued loss of CD4 cells
- inflammatory cytokine-mediated disruption of lymph node-associated immune processing, lymph node architecture, and CD8 effector functions
- evolutionary changes in the virus that result in increased T cell syncytia formation and cell death
continued loss of CD4 cells due to
- viral replication in CD4+ cells
- induction of memory CD4 cell apoptosis
- CTL destruction of virally-infected cells
results in progressive systemic inflammatory activation by pathogens
loss of CD4 mediated protective mechanisms in the gut
many of the CD4 T cells are initially lost from
Peyer’s patches in the gut
apoptosis of uninfected memory CD4 lymphocytes in lymph nodes results from
TLR-induced entry into S-phase (mediated by TLR-7 and TLR-8)
treatment with HAART results in
an increase in CD4 cells
which cells are never recovered even after HAART
HIV-specific CD4 cells
progression of disease is reflected in
absolute peripheral CD4 count
progressive defects in immune function result from
loss of memory T cells (CD4) and disruption of effector T cell (CD8) mediated processes
chronic immune and inflammatory activation of both CD4 and CD8 cell populations results in
- increased viral replication and cell death by cytolysis
- enhanced apoptosis of non-infected cells
- disruption of CD8 effector mechanisms
what does a sticky effector CD8 T cell mean
expression of CD69
CD8 T cells retained within lymph nodes instead of migrating to the periphery to provide protective functions
Two current treatment maxims resulted from evolution of drug-resistant strains
- maximal inhibition of virus replication should result in a decrease in the frequency of drug resistance
- treatment should also include multiple agents
HIV RNA levels are currently used to
diagnose acute infection
follow effectiveness of therapy
indicated breakthrough of virus
predict prognosis in combination with CD4 levels
full blown AIDS is diagnosed when
CD4 count drops below 200/ml
HIV/AIDS infection of the CNS is associated with
subacute meningoencephalitis with a chronic inflammatory infiltrate with microglial nodules and multinucleated giant cells
Associated neoplastic conditions
Kaposi’s sarcoma, Hodgkin’s disease, and lymphoma
Opportunistic infections
- Candidiasis
- Pneumocystis pneumonia
- Cryptococcus
- CMV/Herpes/Zoster
- GI infections (Giardia, amebiasis, cryptosporidiosis)
- reactivation of latents - TB, toxo, herpes zoster
- fungal infections
Kaposi’s sarcoma
masses of proliferative spindle-shaped cells that form blood-filled channels
involves skin, mucous membranes, GI tract
angiogenic and inflammatory cytokines synthesized by virally infected cells appear to drive the vascular proliferation
Non-Hodgkin’s lymphoma
highly aggressive B cell lymphomas
inhibits viral repliation
HAART
