       Document 0596
 DOCN  M9550596
 TI    V3-independent determinants of macrophage tropism in a primary human
       immunodeficiency virus type 1 isolate.
 DT    9505
 AU    Kim FM; Kolson DL; Balliet JW; Srinivasan A; Collman RG; Department of
       Medicine, University of Pennsylvania School of; Medicine, Philadelphia
       19104-6076.
 SO    J Virol. 1995 Mar;69(3):1755-61. Unique Identifier : AIDSLINE
       MED/95156606
 AB    Human immunodeficiency virus type 1 isolates differ in their ability to
       productively infect macrophages, and several groups have mapped the
       genetic basis for macrophage tropism to regions of env that include the
       third hypervariable region (V3 loop). We recently described a primary
       isolate (89.6) which is highly macrophage tropic and yet differs from
       other macrophage-tropic strains studied in that it is cytopathic in T
       cells. Genetic mapping of macrophage tropism determinants in this virus
       was done by using chimeras generated with the prototypic
       non-macrophage-tropic strain HXB2. Replacement of a 2.7-kb
       env-containing region of HXB with corresponding sequences from 89.6
       conferred the macrophage-tropic phenotype, but insertion of the 89.6 V3
       loop along with V4/V5 sequences did not. Conversely, placement of HXB
       sequences that included V3 into 89.6 did not impair this strain's
       ability to replicate in macrophages. Sequence analysis of V3 shows that
       89.6 differs markedly from previously described macrophage-tropic
       consensus sequences and that it is more similar to highly charged
       non-macrophage-tropic strains. This suggests either that macrophage
       tropism is defined by structural determinants resulting from complex
       interactions among multiple env regions rather than V3 sequence-specific
       requirements or that there are multiple mechanisms by which different
       strains may establish productive macrophage infection. In addition,
       because the HXB V3 loop supports productive macrophage infection in the
       background of 89.6, phenotypic characterization of V3 sequences should
       be considered specific to the viral context in which they are placed.
 DE    Amino Acid Sequence  Base Sequence  Chimeric Proteins  Comparative Study
       Consensus Sequence  DNA Primers/CHEMISTRY  Human  HIV Envelope Protein
       gp120/*PHYSIOLOGY  HIV-1/*GROWTH & DEVELOPMENT  In Vitro
       Macrophages/*MICROBIOLOGY  Molecular Sequence Data  Sequence Alignment
       Sequence Homology, Amino Acid  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Virus Replication  JOURNAL ARTICLE

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

