Truncation of the human immunodeficiency virus type 1 envelope glycoprotein allows efficient pseudotyping of moloney murine leukemia virus particles and gene transfer into CD4(+) cells
Truncation of the human immunodeficiency virus type 1 envelope glycoprotein allows efficient pseudotyping of moloney murine leukemia virus particles and gene transfer into CD4(+) cells
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DOI：
10.1128/jvi.71.4.3341-3345.1997
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发表时间：
1997-04-01
影响因子：
5.4
通讯作者：
Gottlinger, HG
中科院分区：
文献类型：
--
作者：
Mammano, F;Salvatori, F;Gottlinger, HG
人类免疫缺陷病毒1型(HIV-1)可以很容易地接受来自远亲逆转录病毒的包膜糖蛋白。然而，我们先前证明，即使从另一种慢病毒Visna病毒的Gag蛋白形成的颗粒中也排除了HIV-1包膜糖蛋白复合体，除非Visna病毒Gag多聚蛋白的基质结构域被HIV-1的基质结构域所取代。我们还发现，HIV-1基质结构域的完整性对于野生型HIV-1 Env蛋白的掺入至关重要，但对于缺少跨膜糖蛋白胞质结构域144个C末端氨基酸的截短形式的掺入并不关键。我们在这里报道，跨膜糖蛋白的C端截断也允许HIV-1Env蛋白有效地掺入由广泛分化的Moloney鼠白血病病毒(Mo-MLV)的Gag蛋白形成的病毒颗粒中。此外，用截短的而不是全长的HIV-I env对基于Mo-MLV的载体进行伪分型，可以有效地转导人类CD4(+)细胞。这些结果表明，基于Mo-MLV的载体可以用于靶向易受HIV-1感染的细胞。
Human immunodeficiency virus type 1 (HIV-1) can readily accept envelope (Env) glycoproteins from distantly related retroviruses. However, we previously showed that the HIV-1 Env glycoprotein complex is excluded even from particles formed by the Gag proteins of another lentivirus, visna virus, unless the matrix domain of the visna virus Gag polyprotein is replaced by that of HIV-1. We also showed that the integrity of the HIV-1 matrix domain is critical for the incorporation of wild-type HIV-1 Env protein but not for the incorporation of a truncated form which lacks the 144 C-terminal amino acids of the cytoplasmic domain of the transmembrane glycoprotein. We report here that the C-terminal truncation of the transmembrane glycoprotein also allows the efficient incorporation of HIV-1 Env proteins into viral particles formed by the Gag proteins of the widely divergent Moloney murine leukemia virus (Mo-MLV). Additionally, pseudotyping of a Mo-MLV-based vector with the truncated rather than the full-length HIV-I Env allowed efficient transduction of human CD4(+) cells. These results establish that Mo-MLV-based vectors can be used to target cells susceptible to infection by HIV-1.