DISTINCT EFFECTS IN PRIMARY MACROPHAGES AND LYMPHOCYTES OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACCESSORY GENES VPR, VPU, AND NEF - MUTATIONAL ANALYSIS OF A PRIMARY HIV-1 ISOLATE
DISTINCT EFFECTS IN PRIMARY MACROPHAGES AND LYMPHOCYTES OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACCESSORY GENES VPR, VPU, AND NEF - MUTATIONAL ANALYSIS OF A PRIMARY HIV-1 ISOLATE
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DOI：
10.1006/viro.1994.1225
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发表时间：
1994-05-01
期刊：
影响因子：
3.7
通讯作者：
COLLMAN, R
中科院分区：
文献类型：
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作者：
BALLIET, JW;KOLSON, DL;COLLMAN, R
巨噬细胞和淋巴细胞是体内产生HIV-1感染的两个主要靶点。为了比较非必需的HIV-1辅助基因VPR、VPU和nef在这些主要细胞类型中对病毒复制的影响，我们从分子克隆的嗜巨噬细胞HIV-1主要分离株中产生了一组突变病毒。突变病毒在巨噬细胞中的复制模式明显不同，而在淋巴细胞中的复制模式差异不大。VPR或VPU的丢失使巨噬细胞中病毒抗原的产生减少了1000倍，而淋巴细胞的复制仅受到轻微影响。NEF的缺失不影响淋巴细胞的感染，但在一定程度上减少了巨噬细胞的复制。多个辅助基因的突变限制了这两种细胞的复制，但在巨噬细胞中的复制程度要大得多，并经常导致非生产性感染。在不同供者的巨噬细胞中，复制依赖于完整的辅助基因的程度有所不同。这些辅助基因在HIV-1感染中的基本功能可能与它们促进巨噬细胞生产性感染的综合作用有关。(C)1994年学术出版社。
Macrophages and lymphocytes are the two main targets for productive HIV-1 infection in vivo. To compare the effects of the ''nonessential'' HIV-1 accessory genes vpr, vpu, and nef on Viral replication in these primary cell types, we generated a panel of mutant viruses derived from a molecularly cloned macrophage-tropic HIV-1 primary isolate. Mutant viruses had markedly different patterns of replication in macrophages, in contrast to lymphocytes in which differences were modest. Loss of vpr or vpu reduced viral antigen production in macrophages by up to 1000-fold, while replication in lymphocytes was only marginally affected. Loss of nef did not affect lymphocyte infection, but decreased replication in macrophages to a small extent. Mutation of multiple accessory genes restricted replication in both cell types, but to a much greater extent in macrophages, and frequently resulted in nonproductive infection. The degree to which replication depended on intact accessory genes varied in macrophages from different donors. The essential functions of these accessory genes in HIV-1 infection may be related to their combined effects in facilitating productive infection of macrophages. (C) 1994 Academic Press, Inc.