Document 0723
 DOCN  M95A0723
 TI    Amino acid substitutions in the V3 loop are responsible for adaptation
       to growth in transformed T-cell lines of a primary human
       immunodeficiency virus type 1.
 DT    9510
 AU    Harrowe G; Cheng-Mayer C; Department of Medicine, University of
       California, San Francisco; 94143-0128, USA.
 SO    Virology. 1995 Jul 10;210(2):490-4. Unique Identifier : AIDSLINE
       MED/95343563
 AB    A T-cell-line-tropic, syncytium-inducing, sCD4- and serum
       neutralization-sensitive variant (R3H) of the macrophage-tropic,
       non-syncytium-inducing, sCD4- and serum neutralization-resistant
       molecular clone HIV-1SF162 was obtained by passage through the T-cell
       line HUT 78. Sequence analyses of the V1-V5 regions of envelope gp120 of
       the variant R3H revealed amino acid substitutions in the V3 (amino acids
       307, 312) and V4 (amino acid 390) domains. Site-directed mutagenesis of
       the HIV-1SF162 genome showed that specific mutations in the V3 loop of
       this isolate can alter tropism and cytopathicity of the virus, but only
       moderately affect its sensitivity to sCD4 and serum neutralization.
       These results show that adaptation to growth in T-cell lines can render
       a primary-like virus sensitive to sCD4 and serum neutralization.
       However, the extent of T-cell line tropism does not correlate with the
       degree of susceptibility to sCD4 and serum neutralization. The latter
       appears to be dependent on the amino acid compositions of the V3 loop
       and other regions of envelope gp120, whereas the former is primarily
       determined by the V3 loop. Our findings further illustrate the
       importance of the V3 loop in influencing HIV-1 cell tropism and
       syncytium formation, and the interplay among V3 loop residues in
       maintaining a structure of the loop that influences biological phenotype
       of the virus.
 DE    Adaptation, Physiological/GENETICS  Amino Acids/*PHYSIOLOGY  Antibodies,
       Monoclonal  Antibodies, Viral  Antigens, CD4  Cell Line, Transformed
       Human  HIV Envelope Protein gp120/*GENETICS  HIV-1/*GROWTH &
       DEVELOPMENT/GENETICS  Immune Sera  Leukocytes, Mononuclear/VIROLOGY
       Macrophages/VIROLOGY  Mutation/PHYSIOLOGY  Neutralization Tests  Peptide
       Fragments/*GENETICS  Recombinant Proteins  Sequence Analysis, DNA
       Serial Passage  Support, U.S. Gov't, P.H.S.  T-Lymphocytes/*VIROLOGY
       JOURNAL ARTICLE

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