       Document 0204
 DOCN  M9610204
 TI    Fusogenic selectivity of the envelope glycoprotein is a major
       determinant of human immunodeficiency virus type 1 tropism for CD4+
       T-cell lines vs. primary macrophages.
 DT    9601
 AU    Broder CC; Berger EA; Laboratory of Viral Diseases, National Institute
       of Allergy and; Infectious Diseases, National Institutes of Health,
       Bethesda, MD; 20892, USA.
 SO    Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):9004-8. Unique Identifier :
       AIDSLINE MED/96004667
 AB    We investigated the relationship between the fusion selectivity of the
       envelope glycoprotein (env) and the tropism of different human
       immunodeficiency virus type 1 (HIV-1) isolates for CD4+ human T-cell
       lines vs. primary macrophages. Recombinant vaccinia viruses were
       prepared encoding the envs from several well-characterized HIV-1
       isolates with distinct cytotropisms. Cells expressing the recombinant
       envs were mixed with various CD4+ partner cell types; cell fusion was
       monitored by a quantitative reporter gene assay and by syncytia
       formation. With CD4+ continuous cell lines as partners (T-cell lines,
       HeLa cells expressing recombinant CD4), efficient fusion occurred with
       the envs from T-cell line-tropic isolates (IIIB, LAV, SF2, and RF) but
       not with the envs from macrophage-tropic isolates (JR-FL, SF162, ADA,
       and Ba-L). The opposite selectivity pattern was observed with primary
       macrophages as cell partners; stronger fusion occurred with the envs
       from the macrophage-tropic than from the T-cell line-tropic isolates.
       All the envs showed fusion activity with peripheral blood mononuclear
       cells as partners, consistent with the ability of this cell population
       to support replication of all the corresponding HIV-1 isolates. These
       fusion selectivities were maintained irrespective of the cell type used
       to express env, thereby excluding a role for differential host cell
       modification. We conclude that the intrinsic fusion selectivity of env
       plays a major role in the tropism of a HIV-1 isolate for infection of
       CD4+ T-cell lines vs. primary macrophages, presumably by determining the
       selectivity of virus entry and cell fusion.
 DE    Cells, Cultured  Comparative Study  CD4-Positive T-Lymphocytes/*VIROLOGY
       Human  HIV-1/*GROWTH & DEVELOPMENT/GENETICS/ISOLATION & PURIF
       Macrophages/*VIROLOGY  Recombinant Proteins/METABOLISM  Support, U.S.
       Gov't, P.H.S.  Vaccinia Virus/GENETICS  Variation (Genetics)  Viral
       Fusion Proteins/GENETICS/*METABOLISM  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

