       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).

