Sayan Murat, Simşek Funda, Ceran Nurgül, Dokuzoğuz Başak, Eraksoy Haluk
Kocaeli University Medical Faculty Hospital, Central Laboratory, PCR Unit, Kocaeli, Turkey.
Mikrobiyol Bul. 2013 Jul;47(3):482-92. doi: 10.5578/mb.5150.
Host genetic factors may play an effective role on the human immunodeficiency virus (HIV) pathogenesis. APOBEC3 (apolipoprotein B mRNA editing enzyme catalytic polypeptide like-3) proteins are cellular antiviral proteins which inhibits HIV replication in the absence of vif (virion infectivity factor). In this study, we aimed to determine the APOBEC 3G/F hypermutations in HIV-1 strains isolated in Turkey. A total of 515 HIV-1 infected patients between June 2009 - February 2012 were included in the study. Three hundred ninety four cases were newly diagnosed antiretroviral-naive patients [349 male, 45 female; median age (range): 37.1 (2-69) years; median CD4+ T-cell count (range): 340 (1-1660) mm3; median HIV-RNA load (range): 5.76 + E5 (8.7 + E2-9.4 + E6) IU/ml] and 121 were under HAART therapy [99 male, 22 female; median age (range): 40.7 (20-70) years; median CD4+ T-cell count (range): 195 (6-720) mm3; median HIV-RNA load (range): 5.4 + E5 (1.37 + E3-1.07 + E7) IU/ml]. APOBEC 3G/F hypermutations in HIV-1 pol sequences (reverse transcriptase; codons 41-238 and protease; codons 1-99) analysed by nested RT-PCR and direct sequencing techniques. APOBEC 3G/F hypermutations have been determined by using of HIVdb-Stanford algorithm. The prevalence of overall APOBEC 3G/F hypermutations was 2.5% (13/515) in HIV-1 pol gene sequences in study group, and the rates were 2% (8/394) and 4.1% (5/121) in antiretroviral naive and treatment groups, respectively. However, the location and marker hypermutations of determined APOBEC in the HIV-1 pol gene sequences were RT and 3G in the Turkish patients. The hypermutated HIV-1 strains identified in HIV-1 infected patients may facilitate our understanding the nature and the consequences of HIV-1 infections. Moreover, investigations of the motif and frequency of APOBEC 3G/F hypermutations in HIV-1 proviral DNA samples and understanding their relationships with HIV-1 subtypes in Turkish patients would be beneficial.
宿主遗传因素可能在人类免疫缺陷病毒（HIV）发病机制中发挥有效作用。载脂蛋白B mRNA编辑酶催化多肽样3（APOBEC3）蛋白是细胞抗病毒蛋白，在缺乏病毒体感染因子（vif）的情况下可抑制HIV复制。在本研究中，我们旨在确定在土耳其分离出的HIV-1毒株中的APOBEC 3G/F超突变。2009年6月至2012年2月期间，共有515例HIV-1感染患者纳入本研究。394例为新诊断的未接受过抗逆转录病毒治疗的患者[男性349例，女性45例；中位年龄（范围）：37.1（2 - 69）岁；中位CD4 + T细胞计数（范围）：340（1 - 1660）/mm³；中位HIV-RNA载量（范围）：5.76 + E5（8.7 + E2 - 9.4 + E6）IU/ml]，121例正在接受高效抗逆转录病毒治疗（HAART）[男性99例，女性22例；中位年龄（范围）：40.7（20 - 70）岁；中位CD4 + T细胞计数（范围）：195（6 - 720）/mm³；中位HIV-RNA载量（范围）：5.4 + E5（1.37 + E3 - 1.07 + E7）IU/ml]。通过巢式RT-PCR和直接测序技术分析HIV-1 pol序列（逆转录酶；密码子41 - 238和蛋白酶；密码子1 - 99）中的APOBEC 3G/F超突变。使用HIVdb-斯坦福算法确定APOBEC 3G/F超突变。研究组HIV-1 pol基因序列中总体APOBEC 3G/F超突变的发生率为2.5%（13/515），在未接受抗逆转录病毒治疗组和治疗组中的发生率分别为2%（8/394）和4.1%（5/121）。然而，在土耳其患者的HIV-1 pol基因序列中确定的APOBEC的位置和标记超突变是逆转录酶（RT）和3G。在HIV-1感染患者中鉴定出的超突变HIV-1毒株可能有助于我们了解HIV-1感染的性质和后果。此外，对土耳其患者HIV-1前病毒DNA样本中APOBEC 3G/F超突变的基序和频率进行研究，并了解它们与HIV-1亚型的关系将是有益的。
