Department of Cell Biology, National Institute for the Control of Pharmaceutical and Biological Products, Beijing, China.
J Acquir Immune Defic Syndr. 2010 Apr 1;53(4):440-50. doi: 10.1097/QAI.0b013e3181cb8300.
Although a great number of HIV-1 pseudoviruses have been generated for neutralization assays, circulating recombinant forms, such as CRF01_AE, are not included. Given the increasing prevalence of CRF01_AE, the establishment of a pool of CRF01_AE env isolates for the evaluation of potential HIV vaccines is needed.
Full-length env genes were cloned from HIV-1 CRF01_AE-infected plasma samples collected in China and used to establish Env-pseudotyped viruses. The neutralization phenotypes of the pseudoviruses were characterized by testing against broadly neutralizing monoclonal antibodies, coreceptor antagonists, and 42 plasma samples that include 3 main prevalent HIV-1 subtypes in China.
Thirty-four genetically distinct CRF01_AE env genes were cloned and used to generate pseudotyped viruses. Of the 34 pseudoviruses, 32 used CCR5 as a coreceptor and 2 used CXCR4. The majority of pseudoviruses were resistant to the neutralizing antibodies IgG1b12 and 2G12 and susceptible to 2F5 and 4E10. There was significant variation of the neutralization susceptibility of pseudoviruses against 42 HIV-1-positive plasma samples. Based on their overall neutralization susceptibilities, the 34 CRF01_AE pseudoviruses were classified into 3 tiers: high, medium, and low.
The CRF01_AE pseudovirus isolates should be included in the panel of pseudoviruses used to assess vaccine-elicited neutralizing antibodies.
尽管已经生成了大量用于中和测定的 HIV-1 假病毒,但并未包括循环重组形式,如 CRF01_AE。鉴于 CRF01_AE 的流行率不断上升,需要建立一个 CRF01_AE 包膜(env)分离株库,以评估潜在的 HIV 疫苗。
从在中国采集的 HIV-1 CRF01_AE 感染的血浆样本中克隆全长 env 基因,并用于建立包膜假病毒。通过测试针对广泛中和的单克隆抗体、核心受体拮抗剂以及包括中国 3 种主要流行 HIV-1 亚型在内的 42 份血浆样本,对假病毒的中和表型进行了特征描述。
从 34 个具有遗传差异的 CRF01_AE env 基因中克隆并用于生成假病毒。在 34 种假病毒中,32 种使用 CCR5 作为核心受体,2 种使用 CXCR4。大多数假病毒对中和抗体 IgG1b12 和 2G12 具有抗性,对 2F5 和 4E10 敏感。假病毒对 42 份 HIV-1 阳性血浆样本的中和敏感性存在显著差异。根据其整体中和敏感性,34 种 CRF01_AE 假病毒被分为 3 个等级:高、中、低。
CRF01_AE 假病毒分离株应包含在用于评估疫苗诱导的中和抗体的假病毒组中。