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.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Balliet, JW; Kolson, DL; Eiger, G; Kim, FM; McGann, KA; Srinivasan, A; Collman, R

Published Date

  • May 1, 1994

Published In

Volume / Issue

  • 200 / 2

Start / End Page

  • 623 - 631

PubMed ID

  • 8178448

Pubmed Central ID

  • 8178448

International Standard Serial Number (ISSN)

  • 0042-6822

Digital Object Identifier (DOI)

  • 10.1006/viro.1994.1225

Language

  • eng

Conference Location

  • United States