Document 0201 DOCN M9460201 TI 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. DT 9408 AU Balliet JW; Kolson DL; Eiger G; Kim FM; McGann KA; Srinivasan A; Collman R; Department of Medicine (Pulmonary and Critical Care Division),; University of Pennsylvania School of Medicine, Philadelphia; 19104-6076. SO Virology. 1994 May 1;200(2):623-31. Unique Identifier : AIDSLINE MED/94233725 AB 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. DE Base Sequence Comparative Study DNA Mutational Analysis Genes, nef/GENETICS Genes, vpr/GENETICS Genes, vpu/GENETICS Genes, Viral/*GENETICS Human HIV-1/*GROWTH & DEVELOPMENT/GENETICS Lymphocytes/*MICROBIOLOGY Macrophages/*MICROBIOLOGY Molecular Sequence Data Mutagenesis Proviruses/GENETICS Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Virus Replication/GENETICS JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).