Document 0404
 DOCN  M9490404
 TI    Cryptic nature of envelope V3 region epitopes protects primary
       monocytotropic human immunodeficiency virus type 1 from antibody
       neutralization.
 DT    9411
 AU    Bou-Habib DC; Roderiquez G; Oravecz T; Berman PW; Lusso P; Norcross MA;
       Division of Hematologic Products, Food and Drug Administration,;
       Bethesda, Maryland 20892.
 SO    J Virol. 1994 Sep;68(9):6006-13. Unique Identifier : AIDSLINE
       MED/94335117
 AB    Characterization of biological and immunological properties of human
       immunodeficiency virus type 1 (HIV-1) is critical to developing
       effective therapies and vaccines for AIDS. With the use of a novel CD4+
       T-cell line (PM-1) permissive to infection by both monocytotropic (MT)
       and T-cell-tropic virus types, we present a comparative analysis of the
       immunological properties of a prototypic primary MT isolate of HIV-1
       strain JR-CSF (MT-CSF) with those of a T-cell-tropic variant (T-CSF) of
       the same virus, which emerged spontaneously in vitro. The parental
       MT-CSF infected only PM-1 cells and was markedly resistant to
       neutralization by sera from HIV-1-infected individuals, rabbit antiserum
       to recombinant MT-CSF gp120, and anti-V3 monoclonal antibodies. The
       T-CSF variant infected a variety of CD4+ T-cell lines, contained
       positively charged amino acid substitutions in the gp120 V3 region, and
       was highly sensitive to antibody neutralization. Neutralization and
       antibody staining of T-CSF-expressing cells were significantly inhibited
       by HIV-1 V3 peptides; in contrast, the MT strain showed only weak
       V3-specific binding of polyclonal and monoclonal antibodies. Exposure of
       PM-1 cells to a mixture of both viruses in the presence of human
       anti-HIV-1 neutralizing antiserum resulted in infection with only
       MT-CSF. These results demonstrate that although the V3 region of MT
       viruses is immunogenic, the target epitopes in the V3 principal
       neutralizing domain on the membrane form of the MT envelope appear to be
       cryptic or hidden from blocking antibodies.
 DE    Amino Acid Sequence  Comparative Study  Consensus Sequence  DNA
       Primers/CHEMISTRY  Human  HIV Antibodies/*IMMUNOLOGY  HIV Envelope
       Protein gp120/*IMMUNOLOGY  HIV-1/*IMMUNOLOGY  In Vitro  Molecular
       Sequence Data  Monocytes/*MICROBIOLOGY  Neutralization Tests  Sequence
       Alignment  Sequence Homology, Amino Acid  Support, U.S. Gov't, P.H.S.
       T-Lymphocytes/MICROBIOLOGY  JOURNAL ARTICLE

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