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M9490404.TXT
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1994-09-19
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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).