ABCC1 p.Val108Ile
Predicted by SNAP2: | A: N (78%), C: N (82%), D: D (71%), E: N (57%), F: N (72%), G: N (57%), H: N (66%), I: N (93%), K: D (53%), L: N (82%), M: N (78%), N: N (61%), P: N (57%), Q: N (72%), R: N (53%), S: N (72%), T: N (82%), W: N (66%), Y: N (82%), |
Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
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[hide] Anti-HIV effects of chloroquine: inhibition of vir... J Acquir Immune Defic Syndr. 2004 Mar 1;35(3):223-32. Savarino A, Lucia MB, Rastrelli E, Rutella S, Golotta C, Morra E, Tamburrini E, Perno CF, Boelaert JR, Sperber K, Cauda R
Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors.
J Acquir Immune Defic Syndr. 2004 Mar 1;35(3):223-32., 2004-03-01 [PMID:15076236]
Abstract [show]
OBJECTIVE: We tested the effects of chloroquine (CQ) on glycosylation of HIV particles and in combination with protease inhibitors (PIs) on HIV replication and on P-glycoprotein (P-gp)/multidrug resistance protein-1 (MRP1). DESIGN: CD4 cell lines were infected with laboratory strains and peripheral blood mononuclear cells were infected with primary isolates for evaluation of the anti-HIV effects. Peripheral blood lymphocytes were evaluated for of P-gp and MRP1 functions. METHODS: HIV replication was assessed by enzyme-linked immunosorbent assay. HIV glycosylation was measured by metabolic labeling of viral particles with [H] glucosamine. Synergism was tested using isobolograms. P-gp and MRP1 functions were assayed using rhodamine 123 (Rh123) and carboxyfluorescein (CF) efflux assays, respectively. RESULTS: CQ alone inhibited HIV replication and glycosylation in a dose-dependent manner. In combination with indinavir (IDV), ritonavir, or saquinavir (SQV), CQ had a synergistic effect at concentrations found in plasma of subjects receiving malaria prophylaxis. CQ decreased the 50% effective concentration of IDV in primary isolates from Africa and restored the response to IDV or SQV in 3 PI-resistant isolates. CQ increased the block of Rh123 and CF efflux activity exerted by PIs. CONCLUSION: The inhibitory effects of CQ on HIV glycosylation are associated with synergistic effects in combination with PIs. The CQ/PI combination exerts combined inhibitory effects on P-gp and MRP1 function.
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No. Sentence Comment
27 The laboratory-adapted HIV-1IIIB and HIV-2CBL/20 strains and the primary isolates HIV-1UG3 (clade A, R5) and HIV-1VI 829 (clade C, R5) from antiretroviral-naive African subjects were obtained as previously described.2,18 HIV-1PAVIA11 and HIV-1PAVIA12 (clade B, coreceptor usage undetermined) were isolated from Italian individuals with highly active antiretroviral therapy (HAART) failure and possess a genotypic profile of multidrug resistance.19 Protease resistance mutations were L10I, M46I, L63P, G73T, V77IV, I84V, and L90M in HIV-1PAVIA11 and L10I, M46L, I54V, L63V, A71T, V82A, and I93L in HIV-1PAVIA12, whereas RT resistance mutations were M41L, E44D, D67N, T69D, K103N, V108I, V118I, M184V, L210W, T215Y, F227FL, and K238KT in HIV-1PAVIA11 and M41L, E44D, D67N, M184V, L210W, and T215Y in HIV-1PAVIA12.
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ABCC1 p.Val108Ile 15076236:27:679
status: NEW