ABCMdb

ABCC8 p.Ile93Leu

Predicted by SNAP2:	A: N (72%), C: N (66%), D: D (71%), E: D (66%), F: N (66%), G: D (53%), H: D (63%), K: D (71%), L: N (93%), M: N (78%), N: D (66%), P: D (71%), Q: N (66%), R: D (66%), S: D (53%), T: N (82%), V: N (93%), W: D (63%), Y: D (53%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D,

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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]

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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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49 The following minor resistance mutations, defined by at least 1 of the 3 algorithms, were found in more than 75% of the sequences: L10V (75%), I15V (91%), E35N (97%), M36I (99%), K43T (75%), Q58E (97%), I62V (100%), I64V (84%), H69R (88%), A71V (94%), L89I (88%), and I93L (100%) (Fig. 1C). Login to comment
113 Furthermore, HIV-OANT70 and HIV-2ROD reference sequences shared 6 resistance-associated mutations (M36I, Q58E, I62V, A71V, L89I, I93L) and 1 uncommon mutation (I13A).25-27 Thus, as for HIV-2,27-29 HIV-O natural polymorphism is likely to have consequences for susceptibility to the different PI. Login to comment