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鉴定包膜V3环为HIV-1 CD4中和敏感性的主要决定因素。

Identification of envelope V3 loop as the major determinant of CD4 neutralization sensitivity of HIV-1.

作者信息

Hwang S S, Boyle T J, Lyerly H K, Cullen B R

机构信息

Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.

出版信息

Science. 1992 Jul 24;257(5069):535-7. doi: 10.1126/science.1636088.

DOI:10.1126/science.1636088
PMID:1636088
Abstract

Laboratory isolates of human immunodeficiency virus type-1 (HIV-1) such as HTLV-IIIB are generally T cell line-tropic and highly sensitive to neutralization by soluble CD4 (sCD4), a potential antiviral agent that is undergoing clinical trial. However, many primary HIV-1 isolates are macrophage-tropic and sCD4-resistant. Envelope V3 loop sequences derived from primary HIV-1 isolates were sufficient to confer on HTLV-IIIB not only the tissue tropism but also the degree of sCD4 neutralization resistance characteristic of their HIV-1 strains of origin. Single amino acid changes in the V3 loop enhanced sCD4 resistance by up to tenfold. These observations suggest that the tissue tropism and sCD4 neutralization sensitivity of HIV-1 isolates are regulated by similar mechanisms.

摘要

1型人类免疫缺陷病毒(HIV-1)的实验室分离株,如HTLV-IIIB,通常嗜T细胞系,并且对可溶性CD4(sCD4)的中和作用高度敏感,sCD4是一种正在进行临床试验的潜在抗病毒药物。然而,许多原发性HIV-1分离株嗜巨噬细胞且对sCD4耐药。源自原发性HIV-1分离株的包膜V3环序列不仅足以赋予HTLV-IIIB其原始HIV-1毒株所特有的组织嗜性,还赋予其sCD4中和抗性程度。V3环中的单个氨基酸变化可将sCD4抗性提高多达十倍。这些观察结果表明,HIV-1分离株的组织嗜性和sCD4中和敏感性受相似机制调控。

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