Turriziani Ombretta, Montagna Claudia, Falasca Francesca, Bucci Mauro, Russo Gianluca, Lichtner Miriam, Sobze Martin Sanou, Vullo Vincenzo, Pistello Mauro, Antonelli Guido
Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
AIDS Res Hum Retroviruses. 2012 Dec;28(12):1729-33. doi: 10.1089/AID.2011.0266. Epub 2012 Mar 2.
Major mutations associated with HIV-I integrase inhibitors (INI) resistance are rare in INI-naive patients. However, polymorphisms at positions that may influence the genetic barrier and/or drive the selection of specific INI resistance pathways are common in HIV non-B subtypes. The aim was to evaluate the presence of natural polymorphisms and/or INI resistance mutations in HIV-1 non-B subtype samples obtained from INI-naive patients living in rural west Cameroon. Thirty-three HIV-1 non-B samples were obtained from INI-naive African women and, as controls, 15 samples of HIV-1 subtype B were obtained from antiretroviral-naive Italian patients. The integrase gene was amplified and sequenced using Trugene Core Reagents. Several amino acid positions in B and non-B subtypes were found to be polymorphic. Interestingly, two patients infected with the CRF02_AG subtype had the resistance mutations N155H and E157Q/E and 12% of African samples had an amino acid substitution at position 143. Silent mutations leading to a higher increment of genetic barriers were detected at 140 and 151 positions in non B-subtypes. Although most polymorphisms may have little effect on INI susceptibility, the IN gene variations found in the present study should be taken into consideration as they may facilitate or delay the emergence of variants fully resistant to INIs.
与HIV-1整合酶抑制剂(INI)耐药相关的主要突变在初治患者中很少见。然而,可能影响遗传屏障和/或推动特定INI耐药途径选择的位点的多态性在HIV非B亚型中很常见。目的是评估从喀麦隆西部农村地区的初治患者获得的HIV-1非B亚型样本中自然多态性和/或INI耐药突变的存在情况。从初治的非洲女性中获得了33份HIV-1非B样本,作为对照,从初治的意大利患者中获得了15份HIV-1 B亚型样本。使用Trugene核心试剂对整合酶基因进行扩增和测序。发现B亚型和非B亚型中的几个氨基酸位点具有多态性。有趣的是,两名感染CRF02_AG亚型的患者具有耐药突变N155H和E157Q/E,12%的非洲样本在第143位有氨基酸替代。在非B亚型的第140和151位检测到导致遗传屏障更高增加的沉默突变。虽然大多数多态性可能对INI敏感性影响不大,但本研究中发现的整合酶基因变异应予以考虑,因为它们可能促进或延迟对INI完全耐药的变异的出现。