ABCC8 p.Val118Cys
| Predicted by SNAP2: | A: N (87%), C: N (78%), D: D (71%), E: D (63%), F: N (82%), G: N (53%), H: N (57%), I: N (97%), K: D (66%), L: N (93%), M: N (82%), N: D (59%), P: D (66%), Q: D (59%), R: D (63%), S: N (61%), T: N (93%), W: D (63%), Y: D (59%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: D, H: N, I: N, K: N, L: N, M: N, N: N, P: D, Q: N, R: N, S: N, T: N, W: N, Y: N, |
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[hide] Impact of HIV-1 group O genetic diversity on genot... J Acquir Immune Defic Syndr. 2011 Feb;56(2):139-45. Depatureaux A, Charpentier C, Leoz M, Unal G, Damond F, Kfutwah A, Vessiere A, Simon F, Plantier JC
Impact of HIV-1 group O genetic diversity on genotypic resistance interpretation by algorithms designed for HIV-1 group M.
J Acquir Immune Defic Syndr. 2011 Feb;56(2):139-45., [PMID:21233638]
Abstract [show]
BACKGROUND: HIV-1 group O (HIV-O) is characterized by a high genetic divergence from HIV-1 group M viruses. Little is known about the therapeutic impact of this diversity. The aim of this study was to assess in a large series of samples (1) the genotypic impact of natural polymorphism of the HIV-O reverse transcriptase and protease genes; and (2) the predictive value of resistance interpretation algorithms developed for HIV-1 group M when used for highly mutated HIV-O viruses. METHODS: Sixty-eight antiretroviral-naive and 9 highly antiretroviral-experienced HIV-O-infected patients were included. The viruses were sequenced and resistance-associated mutations were identified using 3 different algorithms (Agence Nationale de Recherches sur le SIDA et les hepatites virales, Rega, Stanford). RESULTS: All HIV-O samples naturally exhibited the A98G and V179E resistance mutations in the reverse transcriptase region; 54% of samples presented the Y181C mutation, conferring resistance to nonnucleoside reverse transcriptase inhibitors. Twelve minor resistance mutations, present in more than 75% of the protease sequences, led to the different algorithms giving discrepant results for nelfinavir and saquinavir susceptibility. A marked virological response was observed in 8 of the 9 antiretroviral-experienced patients, despite the prediction of limited activity of the combination for 5 to 8 patients according to the algorithm used. CONCLUSIONS: The high level of natural polymorphism in HIV-O genes, and the important discrepancies between genotypic resistance interpretation and the virological response, emphasize the need for resistance algorithm rules better adapted to HIV-O.
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No. Sentence Comment
34 At positions associated with resistance to NRTI, all HIV-O sequenced samples (67 of 67, 100%) harbored the uncommon mutations V118C and L210Y, and 3% (2 of 67) exhibited the T69N mutation (Fig. 1A).
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ABCC8 p.Val118Cys 21233638:34:126
status: NEW104 DISCUSSION We report here a wide range of natural polymorphism in the RT and protease regions in a large series of HIV-O samples issued from 68 ARV-naive patients, extending similar findings previously reported for smaller series.5,11-13,21 The uncommon mutations, V118C and L210Y, were found naturally present in 100% of the RT sequences.
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ABCC8 p.Val118Cys 21233638:104:265
status: NEW106 The phenotypic characteristics of the V118C and L210Y mutants are currently unknown and should be determined to assess their impact on viral susceptibility.
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ABCC8 p.Val118Cys 21233638:106:38
status: NEW