Characterization of Human Endogenous Retroviral Elements in the Blood of HIV-1-Infected Individuals
Characterization of Human Endogenous Retroviral Elements in the Blood of HIV-1-Infected Individuals
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DOI：
10.1128/jvi.00602-11
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发表时间：
2012-01-01
影响因子：
5.4
通讯作者：
Markovitz, David M.
中科院分区：
文献类型：
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作者：
Contreras-Galindo, Rafael;Kaplan, Mark H.;Markovitz, David M.
我们之前报道过，在 HIV-1 感染者和癌症患者的血浆中发现了高滴度的 K 型人内源性逆转录病毒 HERV-K (HML-2) RNA（R. Contreras-Galindo 等人，J. Virol. 82: 9329-9236, 2008.）。 HERV-K (HML-2) 原病毒被激活的程度及其激活的病毒 RNA 的性质仍然是重要的问题。因此，我们对 1 至 3 年内从 7 名 HIV-1 感染者和 5 名乳腺癌患者血浆中收集的 1 型和 2 型 HERV-K (HML-2) 病毒的 env 基因的全长 RNA 进行了扩增和测序，以重建这些病毒的遗传进化。在 HIV-1 患者的血浆组分中发现了 HERV-K (HML-2) RNA，密度约为 1.16 g/ml，其中包含未成熟且正确加工的 HERV-K (HML-2) 蛋白和可被抗 HERV-K (HML-2) 抗体识别的病毒样颗粒。发现了新型 HERV-K (HML-2) 原病毒的 RNA 序列，其中包括 K111，它在 HIV-1 感染期间特别活跃。病毒RNA源自完整的原病毒和缺乏5'长末端重复的原病毒，表明这些患者中HERV-K (HML-2) RNA的表达可能涉及有义和反义转录。在 HIV-1 感染者中，HERV-K (HML-2) 病毒 RNA 显示出频繁重组、同义而非同义突变积累以及保守的 N-糖基化位点的证据，表明一些 HERV-K (HML-2) 病毒 RNA 已经历逆转录并处于纯化选择之下。相比之下，在乳腺癌患者血液中发现的 HERV-K (HML-2) RNA 序列没有显示重组的证据，仅表现出零星的病毒突变。这项研究表明，HERV-K (HML-2) 在 HIV-1 感染患者中具有活性，由此产生的 RNA 信息揭示了之前未被发现的 HERV-K (HML-2) 基因组序列。
We previously reported finding the RNA of a type K human endogenous retrovirus, HERV-K (HML-2), at high titers in the plasma of HIV-1-infected and cancer patients (R. Contreras-Galindo et al., J. Virol. 82: 9329-9236, 2008.). The extent to which the HERV-K (HML-2) proviruses become activated and the nature of their activated viral RNAs remain important questions. Therefore, we amplified and sequenced the full-length RNA of the env gene of the type 1 and 2 HERV-K (HML-2) viruses collected from the plasma of seven HIV-1-infected patients over a period of 1 to 3 years and from five breast cancer patients in order to reconstruct the genetic evolution of these viruses. HERV-K (HML-2) RNA was found in plasma fractions of HIV-1 patients at a density of similar to 1.16 g/ml that contained both immature and correctly processed HERV-K (HML-2) proteins and virus-like particles that were recognized by anti-HERV-K (HML-2) antibodies. RNA sequences from novel HERV-K (HML-2) proviruses were discovered, including K111, which is specifically active during HIV-1 infection. Viral RNA arose from complete proviruses and proviruses devoid of a 5' long terminal repeat, suggesting that the expression of HERV-K (HML-2) RNA in these patients may involve sense and antisense transcription. In HIV-1-infected individuals, the HERV-K (HML-2) viral RNA showed evidence of frequent recombination, accumulation of synonymous rather than nonsynonymous mutations, and conserved N-glycosylation sites, suggesting that some of the HERV-K (HML-2) viral RNAs have undergone reverse transcription and are under purifying selection. In contrast, HERV-K (HML-2) RNA sequences found in the blood of breast cancer patients showed no evidence of recombination and exhibited only sporadic viral mutations. This study suggests that HERV-K (HML-2) is active in HIV-1-infected patients, and the resulting RNA message reveals previously undiscovered HERV-K (HML-2) genomic sequences.