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
- PMID: 8178448
- DOI: 10.1006/viro.1994.1225
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
Abstract
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.
Similar articles
-
Functional analysis of the vpx, vpr, and nef genes of simian immunodeficiency virus.J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Apr 1;8(4):335-44. J Acquir Immune Defic Syndr Hum Retrovirol. 1995. PMID: 7882097
-
Construction and characterization of an HIV-1 group O infectious molecular clone and analysis of vpr- and nef-negative derivatives.Virology. 2004 Sep 1;326(2):329-39. doi: 10.1016/j.virol.2004.05.027. Virology. 2004. PMID: 15321704
-
Persistent infection of MT-4 cells by human immunodeficiency virus type 1 becomes increasingly likely with in vitro serial passage of wild-type but not nef mutant virus.J Gen Virol. 1994 Sep;75 ( Pt 9):2241-51. doi: 10.1099/0022-1317-75-9-2241. J Gen Virol. 1994. PMID: 7521392
-
[The function of accessory genes of HIV-1].Nihon Rinsho. 2002 Apr;60(4):674-80. Nihon Rinsho. 2002. PMID: 11968772 Review. Japanese.
-
HIV-1 replication in CD4+ T cell lines: the effects of adaptation on co-receptor use, tropism, and accessory gene function.J Leukoc Biol. 2000 Sep;68(3):331-7. J Leukoc Biol. 2000. PMID: 10985248 Review.
Cited by
-
The HIV-1 protein Vpr targets the endoribonuclease Dicer for proteasomal degradation to boost macrophage infection.Virology. 2013 Sep;444(1-2):191-202. doi: 10.1016/j.virol.2013.06.010. Epub 2013 Jul 9. Virology. 2013. PMID: 23849790 Free PMC article.
-
Vpr Is a VIP: HIV Vpr and Infected Macrophages Promote Viral Pathogenesis.Viruses. 2020 Jul 27;12(8):809. doi: 10.3390/v12080809. Viruses. 2020. PMID: 32726944 Free PMC article. Review.
-
Limelight on two HIV/SIV accessory proteins in macrophage infection: is Vpx overshadowing Vpr?Retrovirology. 2010 Apr 9;7:35. doi: 10.1186/1742-4690-7-35. Retrovirology. 2010. PMID: 20380700 Free PMC article. Review.
-
Nuclear import of the preintegration complex is blocked upon infection by human immunodeficiency virus type 1 in mouse cells.J Virol. 2007 Jan;81(2):677-88. doi: 10.1128/JVI.00870-06. Epub 2006 Nov 1. J Virol. 2007. PMID: 17079325 Free PMC article.
-
Vpr Enhances HIV-1 Env Processing and Virion Infectivity in Macrophages by Modulating TET2-Dependent IFITM3 Expression.mBio. 2019 Aug 20;10(4):e01344-19. doi: 10.1128/mBio.01344-19. mBio. 2019. PMID: 31431548 Free PMC article.
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
