Term
What does reverse transcriptase do? |
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Definition
converts ssRNA into ssDNA then to ds DNA (integration of viral genome into host DNA) |
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Term
What are the four subfamilies of retroviruses? |
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Definition
lentivirus, oncovirus, spumavirus, and endogenous retrovirus |
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Term
What are the four subfamilies of retroviruses? |
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Definition
lentivirus, oncoviruses, spumaviruses, endogenous retroviruses |
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Term
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Definition
human endogenous retroviruses. retrovirus sequence integrated into the human genome and transmitted vertically (~1% of the human genome) |
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Term
T/F HERVs can produce infectious particles. |
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Definition
false, although some have open reading frames capable of encoding functional proteins |
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Term
Where is the HERV-W envelope protein expressed? What is it's purpose? |
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Definition
human placenta (syncytin protein); essential to create and maintain the syncytiotrophoblast layer between maternal and fetal circulation (essentially a retroviral fusion and entry protein) |
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Term
How does syncytin mediate fusion? |
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Definition
exactly the same was as influenza, measles, HIV, Ebola, lassa fever, and sars! binding induces the N and C helices to clamp together and the hyrdophobic fusion and aromatic peptides cooperate to induce cell fusion |
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Term
What is an example of a human spumavirus? |
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Definition
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Term
What is an example of a human oncovirus? |
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Definition
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Term
What are examples of human lentivirus? |
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Definition
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Term
Describe the genome and outer covering of retroviruses. |
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Definition
icosahedral, envelolped with two identical copies of single-stranged + RNA |
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Term
What is the general genetic organization of retroviruses? |
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Definition
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Term
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Definition
group-specific antigen gene; encodes capsid, nucleocapsid and matrix proteins |
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Term
What is the pol gene for? |
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Definition
polymerase gene; encodes the enzymes reverse transcriptase, protease and integrase |
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Term
What is the env gene for? |
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Definition
envelope gene; encodes surface and transmembrane proteins |
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Term
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Definition
long terminal repeats; gene sequences that bind cellular and viral transcription factors (promoters and enhancers) |
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Term
How does HIV progeny exit the host cell? |
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Definition
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Term
What happens to the retroviral genome after entry to host cell? |
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Definition
linear viral RNA is reverse-transcribed ds DNA circle in the cytoplasm. After nuclear localization, genome integrates into host genome via LTRs and integrase |
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Term
Where does retroviral RNA replication occur? |
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Definition
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Term
When are teh LTRs generated? |
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Definition
after retroviral RNA replication in teh cytoplasm |
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Term
What's another name for the viral genome once it is part of the host genome? |
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Definition
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Term
T/F Spumaviruses can be oncogenic. |
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Definition
false! but they do establish persistent infections |
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Term
T/F Spumaviruses have been isolated only from humnas. |
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Definition
false! isolated from many animal species including humans |
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Term
What is the diseaes caused by spumaviruses? |
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Definition
considered non-pathologic/no disease associated in humnas |
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Term
Describe the distinct cytopathology of spumaviruses. |
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Definition
foamy or lace-like appearance and are often accompanied by syncytium formation |
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Term
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Definition
retroviruses that immortalize or transform cells. Have different core and capsid morphology. May contain growth -regulating oncogenes (sis, ras, src, mos, myc,jun, fos) which are almost identical to the cellular porteins involved in celllular growth control. |
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Term
HTLV causes what diseases? |
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Definition
adult T cell leukemia and tropical spastic paraparesis |
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Term
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Definition
southern Japan and the Caribbean |
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Term
How is HTLV-1 transmitted? |
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Definition
Transmission requires cell to cell contact: sexually, mother-to-infant (breast feeding), IVDU |
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Term
How long after infection does HTLV-1 cause cancer? |
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Definition
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Term
What percent of HTLV-1 infected people get ATLL? |
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Definition
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Term
Name the non-neoplastic neurologic d/os caused by HTLV-1. |
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Definition
HTLV-1 associated myelopathy (tropical spastic paraparesis) or HTLV-1-associated myelopathy (HAM) (this is a demyelinating diseaes of the brain and spinal cord-motor neurons) |
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Term
What oncogene does HTLV contain? |
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Definition
HTLV doesnt have an oncogene, instead it has "tax" a transcriptional regulator (binds in LTR). Also, activates specific cellular genes (IL-2 and GMCSF) to promote outgrowth of that cell. |
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Term
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Definition
multilobulated lymphocytes seen in the blood smear of patients with adult T cell leukemia caused by HTLV-1 |
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Term
Describe the surface, transmembrane, matrix, capsid and nucleocapsid proteins of HTLV-1 virion. |
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Definition
surface- gp 46 transmembrane- gp 21 matrix- p19 capsid- p24 nucleocapsid is p15 |
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Term
Where is HTLV-II prevalent? |
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Definition
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Term
What diseases are associated with HTLV-II? |
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Definition
its unclear; some neurologic and chronic pulmonary d/os |
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Term
Where is HTLV-3 and 4 found? |
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Definition
small number of patients in Cameroon |
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Term
How do you diagnose HTLV? |
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Definition
EIA- detection of antibodies against viral antigens; there is cross-reactivity between HTLV I and II |
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Term
How do you treat HTLV infection? |
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Definition
ATLL (anti cancer therapy) HAM/TSP (antiretrovirals) |
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Term
What characterizes lentiviruses? |
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Definition
slow onset of disease and neurologic d/os and immunosuppression |
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Term
What are some nonhuman examples of lentiviruses? |
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Definition
SIV, visna virus (sheep), caprine arthritis/encephalitis virus (goats) |
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Term
What is the matrix protein of HIV? |
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Definition
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Term
What is the envelop protein of HIV? |
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Definition
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Term
What is the matrix and capsid protein of HIV? |
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Definition
matrix: p17, capsid is p24 |
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Term
Which HIV is less virulent? |
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Definition
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Term
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Definition
sporadic cases currently outside of west africa |
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Term
Are the antigens to HIV-1 the same as those to HIV-2? |
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Definition
core antigens cross-react but envelope antigens to not |
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Term
What virus did HIV-2 originate from? |
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Definition
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Term
When are gag and gag-pol peptides cleaved? |
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Definition
following release of the virion from the cell |
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Term
Which enzymes are located in the HIV virion? |
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Definition
reverse transcriptase and integrase |
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Term
What are the functions of reverse transcriptase? |
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Definition
RNA-dependent DNA polymerase, polypurine endonuclease, RNA-DNA hybrid RNase, ssDNA-dependent DNA polymerase |
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Term
Is reverse transcriptase a dimer, trimer, or tetramer? |
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Definition
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Term
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Definition
true! gp 160 precursor proteins are cleaved by cellular proteases and assembled as trimers |
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Term
How many glycosylation sites are in gp 120? |
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Definition
30-38 N-linked glycosylation sites |
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Term
What are the essential regulator genes of HIV? |
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Definition
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Term
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Definition
protein that is positive regulator of transcription by control of elongation by RNA polymerase II |
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Term
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Definition
protein that regulates exprsesion of viral mRNA for structural genes. Binds to RRE and promotes the nuclear export, stabalization, and utilization of the viral mRNAs containing RRE |
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Term
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Definition
regulatory gene of HIV that produces a protein needed for high levels of virus associated with disease progression; down-regulates CD4 and MHC class I molecules. Not necessary for replication but necessary for disease |
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Term
What are the "accessory" genes of HV? |
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Definition
vif, vpr, vpu (HIV1 only), and vpx (HIV2 only) |
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Term
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Definition
viral infectivity factor; required for HIV-1 replication in primary cells; prevents the action of the cellular APOBEC-3G protein, which deaminates DNA:RNA heteroduplexes in the cytoplasm |
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Term
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Definition
proposed functions include targeting nulcear import of preintegration complexes, cell growth arrest, transactivation of cellular genes, and induction of cellular differentiation |
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Term
What is the function of vpu? |
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Definition
integral membrane protein; degrades CD4 in ER and enhances virion release |
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Term
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Definition
homolog of HIV-1 vpr (integral membrane protein; degrades CD4 in ER, and enhances virion release) |
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Term
Breifly describe the HIV replication cycle. |
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Definition
1) atatchment 2) fusion 3-4) RT--dsDNA 5) transport to nucleus 6) integration 7) viral mRNA 8-9) viral proteins 10) assembly of virions 11) protease cleavage-mature particles |
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Term
What is the risk of infection per sexual encounter with an HIV+ individual? |
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Definition
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Term
Why are some people resistant to HIV infection? |
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Definition
sex workers have some unkown immune response and other individuals have a non-functional CCR5 protein receptor |
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Term
What percent of caucasians have the CCR5 deletion? |
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Definition
10% heterozygous, 1% homozygous |
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Term
What immune dysfunctions are associated with the CCR-5 mutation? |
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Definition
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Term
What are two independent predictors of AIDS progression? |
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Definition
CD4+ T cell count and viral load |
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Term
What dictates the kinetics of the CD4+ T cell decline and time to development of clinical AIDS? |
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Definition
the viral set point after acute infection |
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Term
Where is the AIDS virus at the time of acute HIV syndrome? |
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Definition
widely disseminated, seeding of lymphoid organs |
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Term
How do you tell if an HIV+ pt has AIDS? |
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Definition
clinical component + immunologic component |
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Term
HIV infection destroys massive amounts of CD4 cells each day before symptoms manifest? |
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Definition
true, body is able to keep up but gradual overall loss of CD4 cells eventually will lead to immune dysfunction |
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Term
T/F > 90% of CD4+ cells are infected by HIV. |
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Definition
False! Altho >90% are destroyed by HIV, significantly less are actually infected. |
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Term
How does HIV kill CD4 T cells? |
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Definition
syncytia formation (on infected cell can fuse with unifected cells) and apoptosis |
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Term
How does HIV kill CD4 T cells? |
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Definition
syncytia formation (on infected cell can fuse with unifected cells) and apoptosis |
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Term
How does HIV evade CTL response and antibody response? |
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Definition
exiting as a quasispecies= antigenic drift of gp 120 (highly variable regions of envelope) and glycosylation of gp 120 |
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Term
CD4 loss in HIV infection is mainly due to... |
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Definition
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Term
How does HIV causes apoptosis of CD4 cells and other cells? |
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Definition
pro-apoptotic HIV proteins, apoptosis induced by death receptors, massive apopuosis in GALT releases circulating microbial products that causes apoptosis |
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Term
Which HLA types are associated with slower AIDS disease progression? |
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Definition
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Term
How do you define an AIDS long term non progressor/elite controller? |
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Definition
no clinical evidence of progression in > 10 years. Patients have low viral loads and high CD4 cell counts. Lymph node architecture is intact and have vigorous CD8+ cytotoxic T cells against HIV. Have elevated titers of neutralizing antibodies |
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Term
Whta does NRTI stand for? NNRTI? |
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Definition
nucleoside analog reverse transcriptase inhibitor (NRTI) non-nucleoside analog reverse trancriptase inhibitors (NNRTI) |
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Term
What are the different classes of antiretrovirals? |
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Definition
CCR5 inhibitors, fusion inhibitor, NRTI, NNRTI, integrase inhibitor, protease inhibitor |
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Term
What are the major limitations of nucleoside analogs? |
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Definition
their toxicity, lack of activity in some cell types, and susceptibility to viral resistance |
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Term
What two drugs used in combination are the most effective anti-HIV therapies developed to date? |
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Definition
protease inhibitors used in combination with reverse transcriptase inhibitors (NRTI and NNRTI) |
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Term
Why are HIV drugs used in combination with each other? |
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Definition
substantially reduces the likelihood of protease or multiple-resistant HIV strains developing |
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Term
What was the Merck Vaccine Trial (STEP)? |
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Definition
adenovirus vector with gag, pol adn nef. Did not prevent HIV1 infection or reduce viral loads in those infected |
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Term
What was the THailand study HIV vaccine? |
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Definition
canarypox vector- prime boost strategy with 6 immunizations over 6 months. ALVAC-HIV canarypox vector with HIV env, gag and pro. AIDSVAX-B/E is composed of geneically engineered gp 120, subtypes B adn E |
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Term
What is pre-exposure HIV prophylaxis? |
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Definition
once daily tenofovir or once daily tenofovir plus emtricitabine (NRTI) |
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