表达嵌合型HIV-1 Nef/SIVmac Nef蛋白的嵌合型猿猴-人类免疫缺陷病毒的特性

Properties of a chimeric simian-human immunodeficiency virus expressing an hybrid HIV-1 Nef/SIVmac Nef protein.

作者信息

Bertsch C, Cluet D, Beyer C, Gloeckler L, Cecile A, Gut J P, Aubertin A M

机构信息

INSERM U544, Institut de Virologie, Université Louis Pasteur, Strasbourg, France.

出版信息

Arch Virol. 2002 Oct;147(10):1963-75. doi: 10.1007/s00705-002-0857-8.

DOI:10.1007/s00705-002-0857-8

PMID:12376757

Abstract

The nef genes of human and simian immunodeficiency viruses code for a membrane associated protein critical for AIDS development. SIVmac Nef presents C-terminal a 27 amino acid extension absent of HIV-1 Nef. To estimate the influence of this C-terminal domain on virus properties, we constructed viruses derived from SIVmac239 by replacing SIV nef with HIV-1 Lai nef gene (SHIV NefLai4) or with a sequence encoding a Nef fusion protein: HIV-1 Lai Nef/SIV Nef-Cterm (SHIV-Cterm). The recombinant viruses replicated efficiently in vitro in CEMx174 cells and in activated macaque PBMCs. The addition of SIV Nef C-terminal domain to HIV-1 Nef in SHIVNefLai4 did not change the in vitro properties of the chimeric virus, both viruses being more infectious than a nef deleted virus. Although the half-life of Nef fusion protein was augmented, SHIV-Cterm remained slightly less infectious than SIVmac239.

摘要

人类免疫缺陷病毒和猿猴免疫缺陷病毒的nef基因编码一种对艾滋病发展至关重要的膜相关蛋白。猴免疫缺陷病毒（SIVmac）Nef在C端有一段27个氨基酸的延伸序列，而HIV-1 Nef没有。为了评估这个C端结构域对病毒特性的影响，我们构建了源自SIVmac239的病毒，用HIV-1 Lai nef基因（SHIV NefLai4）或编码Nef融合蛋白的序列：HIV-1 Lai Nef/SIV Nef-Cterm（SHIV-Cterm）替换SIV nef。重组病毒在体外CEMx174细胞和活化的猕猴外周血单核细胞（PBMCs）中能高效复制。在SHIVNefLai4中，将SIV Nef的C端结构域添加到HIV-1 Nef上并没有改变嵌合病毒的体外特性，两种病毒都比nef缺失的病毒更具感染性。虽然Nef融合蛋白的半衰期延长了，但SHIV-Cterm的感染性仍略低于SIVmac239。