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分子克隆的SHIV-CN97001:一种具有复制能力的R5型猿猴/人类免疫缺陷病毒,其env基因来自一株中国HIV-1 C亚型原发分离株。

Molecularly cloned SHIV-CN97001: a replication-competent, R5 simian/human immunodeficiency virus containing env of a primary Chinese HIV-1 clade C isolate.

作者信息

Liu Qiang, Li Yue, Yang GuiBo, Dai JieJie, Ruprecht Ruth M, Shao Yiming

机构信息

National Center for AIDS/STD Control and prevention, China CDC, Beijing, China.

出版信息

J Med Primatol. 2011 Dec;40(6):427-36. doi: 10.1111/j.1600-0684.2011.00497.x. Epub 2011 Sep 6.

Abstract

BACKGROUND

The increasing prevalence of human immunodeficiency virus type 1 (HIV-1) subtype C infection worldwide calls for efforts to develop a relevant animal model for evaluating AIDS candidate vaccines. In China, the prevalent HIV strains comprise a circulating recombinant form, BC (CRF07_BC), in which the envelope belongs to subtype C.

METHODS

To evaluate potential AIDS vaccines targeting Chinese viral strains in non-human primate models, we constructed a simian/human immunodeficiency virus (SHIV) carrying most of the envelope sequence of a primary HIV-1 clade C strain isolated from an HIV-positive intravenous drug user from YunNan province in China. Furthermore, to determine whether in vivo adaptation would enhance the infectivity of SHIV-CN97001, the parental infectious strain was serially passaged through eight Chinese rhesus macaques.

RESULTS

Infection of six Chinese rhesus macaques with SHIV-CN97001 resulted in a low level of viremia and no significant alteration in CD4+ T-lymphocyte counts. However, the hallmarks of SHIV infectivity developed gradually, as shown by the increasingly elevated peak viremia with each passage.

CONCLUSION

These findings establish that the R5-tropic SHIV-CN97001/Chinese rhesus macaque model should be very useful for the evaluation of HIV-1 subtype C vaccines in China.

摘要

背景

全球人类免疫缺陷病毒1型(HIV-1)C亚型感染的患病率不断上升,这就需要努力开发一种相关动物模型来评估艾滋病候选疫苗。在中国,流行的HIV毒株包括一种循环重组形式,即BC(CRF07_BC),其包膜属于C亚型。

方法

为了在非人灵长类动物模型中评估针对中国病毒株的潜在艾滋病疫苗,我们构建了一种猿猴/人类免疫缺陷病毒(SHIV),它携带了从中国云南省一名HIV阳性静脉吸毒者分离出的一株主要HIV-1 C亚型毒株的大部分包膜序列。此外,为了确定体内适应性是否会增强SHIV-CN97001的感染性,将亲代感染性毒株在中国恒河猴中连续传代八次。

结果

用SHIV-CN97001感染六只中国恒河猴,导致病毒血症水平较低,CD4+T淋巴细胞计数无显著变化。然而,SHIV感染性的特征逐渐显现,每次传代时病毒血症峰值越来越高就表明了这一点。

结论

这些发现表明,R5嗜性的SHIV-CN97001/中国恒河猴模型对于评估中国的HIV-1 C亚型疫苗应该非常有用。

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