J.W. Goethe University Hospital, Institute for Med. Virology, Paul Ehrlich Str. 40, 60596 Frankfurt, Germany.
Eur J Med Res. 2010 Oct 25;15(10):415-21. doi: 10.1186/2047-783x-15-10-415.
replication of HIV-1 after cell entry is essentially dependent on the reverse transcriptase (RT). Antiretroviral drugs impairing the function of the RT currently aim at the polymerase subunit. One reason for failure of antiretroviral treatment is the evolvement of resistance-associated mutations in the viral genome. For RT inhibitors, almost all identified mutations are located within the polymerase; therefore, general genotyping confines to investigate this subunit. Recently several studies have shown that substitutions within the RNase H and the connection domain increase antiviral drug-resistance in vitro, and some of them are present in patient isolates.
the aim of the present study was to investigate the prevalence of these substitutions and their association with mutations in the polymerase domain arising during antiretroviral treatment.
we performed genotypic analyzes on seventy-four virus isolates derived from treated and untreated patients, followed at the HIV Centre of the Johann Wolfgang Goethe University Hospital (Frankfurt/Main, Germany). We subsequently ana?lysed the different substitutions in the c-terminal region to evaluate whether there were associations with each other, n-terminal substitutions or with antiretroviral treatment.
We identified several primer grip substitutions, but almost all of them were located in the connection domain. This is consistent with other in-vivo studies, in which especially the primer grip residues located in the RNase H were unvaried. Furthermore, we identified other substitutions in the connection domain and in the RNase H. Especially E399D seemed to be associated with an antiretroviral treatment and N-terminal resistance-delivering mutations.
some of the identified substitutions were associated with antiviral treatment and drug resistance-associated mutations. Due to the low prevalence of C-terminal mutations and as only a few of them could be associated with antiviral treatment and N-terminal resistance-delivering mutations, we would not recommend routinely testing of the C-terminal RT region.
HIV-1 复制在细胞进入后主要依赖于逆转录酶（RT）。目前，损害 RT 功能的抗逆转录病毒药物针对聚合酶亚基。抗逆转录病毒治疗失败的一个原因是病毒基因组中出现与耐药相关的突变。对于 RT 抑制剂，几乎所有鉴定出的突变都位于聚合酶内；因此，一般的基因分型仅限于研究该亚基。最近的几项研究表明，RNase H 和连接域内的取代会增加体外抗病毒药物的耐药性，其中一些存在于患者分离株中。
本研究旨在调查这些取代的流行率及其与抗逆转录病毒治疗过程中聚合酶域中出现的突变之间的关系。
我们对来自接受和未接受治疗的患者的 74 个病毒分离株进行了基因分型分析，这些患者在德国法兰克福歌德大学医院的 HIV 中心接受了治疗。随后，我们分析了 C 末端区域的不同取代，以评估它们彼此之间、N 末端取代或与抗逆转录病毒治疗之间是否存在关联。
我们发现了几个引物夹取代，但几乎所有的取代都位于连接域。这与其他体内研究一致，在这些研究中，位于 RNase H 中的引物夹残基几乎没有变化。此外，我们还在连接域和 RNase H 中发现了其他取代。特别是 E399D 似乎与抗逆转录病毒治疗和 N 末端耐药相关突变有关。
一些鉴定出的取代与抗病毒治疗和耐药相关突变有关。由于 C 末端 RT 区突变的发生率较低，并且只有少数突变与抗病毒治疗和 N 末端耐药相关突变有关，因此我们不建议常规检测 C 末端 RT 区。
