Martins Angélica N, Arruda Mônica B, Pires Ana F, Tanuri Amilcar, Brindeiro Rodrigo M
Molecular Virology Laboratory, Department of Genetics, Federal University of Rio de Janeiro, Brazil.
AIDS Res Hum Retroviruses. 2011 Jun;27(6):687-92. doi: 10.1089/aid.2010.0282. Epub 2011 Jan 23.
HIV-1 budding requires short peptide motifs in p6(Gag), known as late domains, that promote the release of infectious virions. The primary late domain of HIV-1 is a Pro-(Thr/Ser)-Ala-Pro (hereafter referred to as a PTAP) motif. This motif may be completely or partially duplicated. In this work we analyzed p6(Gag) sequences from 547 isolates from drug-naive patients and 213 isolates from patients failing HAART therapy. Complete duplications within PTAP were selected during HAART therapy in all HIV-1 subtypes analyzed: B (p = 0.0338), F1 (p = 0.0294), and C (p = 0.0001). Nevertheless, the patterns of these duplications were different; subtype C isolates accumulated longer duplications and displayed a higher frequency of duplications in both treated (54%) and drug-naive isolates (23%). Accumulation of PTAP duplications within subtypes B, F1, and C during therapy suggests a potential role of the duplications in antiretroviral drug resistance.
HIV-1出芽需要p6（Gag）中的短肽基序，即晚期结构域，以促进感染性病毒粒子的释放。HIV-1的主要晚期结构域是脯氨酸-（苏氨酸/丝氨酸）-丙氨酸-脯氨酸（以下简称PTAP）基序。该基序可能会完全或部分重复。在这项研究中，我们分析了来自未接受过治疗的患者的547株分离株和接受高效抗逆转录病毒治疗（HAART）失败的患者的213株分离株的p6（Gag）序列。在所有分析的HIV-1亚型（B型，p = 0.0338；F1型，p = 0.0294；C型，p = 0.0001）的HAART治疗期间，PTAP内出现了完全重复。然而，这些重复的模式有所不同；C型分离株积累了更长的重复序列，并且在接受治疗的分离株（54%）和未接受过治疗的分离株（23%）中重复频率都更高。治疗期间B型、F1型和C型亚型内PTAP重复序列的积累表明这些重复在抗逆转录病毒药物耐药性中可能发挥作用。
