Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To initiate infection, HIV-1 requires a primary receptor, CD4, and a secondary receptor, principally the chemokine receptor CCR5 or CXCR4. Coreceptor usage plays a critical role in HIV-1 disease progression. HIV-1 transmitted in vivo generally uses CCR5 (R5), but later CXCR4 (X4) strains may emerge; this shift heralds CD4+ cell depletion and clinical deterioration. We asked whether antiretroviral therapy can shift HIV-1 populations back to R5 viruses after X4 strains have emerged, in part because treatment has been successful in slowing disease progression without uniformly suppressing plasma viremia. We analyzed the coreceptor usage of serial primary isolates from 15 women with advanced disease who demonstrated X4 viruses. Coreceptor usage was determined by using a HOS-CD4+ cell system, biological and molecular cloning, and sequencing the envelope gene V3 region. By constructing a mathematical model to measure the proportion of virus in a specimen using each coreceptor, we demonstrated that the predominant viral population shifted from X4 at baseline to R5 strains after treatment. Multivariate analyses showed that the shift was independent of changes in plasma HIV-1 RNA level and CD4+ cell count. Hence, combination therapy may lead to a change in phenotypic character as well as in the quantity of HIV-1. Shifts in coreceptor usage may thereby contribute to the clinical efficacy of anti-HIV drugs.
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PMID:Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy. 1118 42

The tat, rev, vpu, and env genes from the monocytotropic CCR5-dependent HIV-1 Ba-L isolate were substituted for homologous simian immunodeficiency virus (SIV) sequences in the SIV genome. The resultant SHIV (SHIV Ba-L) replicated in CCR5-positive PM-1 cells but not in CCR5-negative CEMX174 cells. Infection of HOS cells expressing different co-receptors showed SHIV Ba-L to be strictly CCR5-dependent. Infection of PM-1 cells and rhesus peripheral blood mononuclear cells (PBMCs) was highly sensitive to RANTES but not to SDF-1. Although SHIV Ba-L infected rhesus and pigtail macaques intravenously or rectally, plasma viremia was controlled after 3 weeks. After serial passage through 4 pigtails by blood and bone marrow transfer, virus from pigtail PBMCs had higher in vitro infectious titers on rhesus PBMCs and was efficiently transmitted vaginally in rhesus and cynomolgus macaques. Plasma viremia generally persisted longer than after infection with unpassaged virus but was eventually controlled with no significant decrease in CD4+ T-cell counts in peripheral blood. The envelope gene of SHIV Ba-L revealed a very little genetic drift during in vivo passage. SHIV Ba-L provides a potentially useful model for R5 HIV-1 infection of humans.
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PMID:Characterization of a simian human immunodeficiency virus encoding the envelope gene from the CCR5-tropic HIV-1 Ba-L. 1284 40