       Document 0781
 DOCN  M9590781
 TI    Replicative function and neutralization sensitivity of envelope
       glycoproteins from primary and T-cell line-passaged human
       immunodeficiency virus type 1 isolates.
 DT    9509
 AU    Sullivan N; Sun Y; Li J; Hofmann W; Sodroski J; Dana-Farber Cancer
       Institute, Department of Pathology, Harvard; Medical School, Boston,
       Massachusetts 02115, USA.
 SO    J Virol. 1995 Jul;69(7):4413-22. Unique Identifier : AIDSLINE
       MED/95287498
 AB    The structure, replicative properties, and sensitivity to neutralization
       by soluble CD4 and monoclonal antibodies were examined for molecularly
       cloned envelope glycoproteins derived from human immunodeficiency virus
       type 1 (HIV-1) viruses either isolated directly from patients or
       passaged in T-cell lines. Complementation of virus entry into peripheral
       blood mononuclear cell targets by primary patient envelope glycoproteins
       exhibited efficiencies ranging from that observed for the HXBc2 envelope
       glycoproteins, which are derived from a T-cell line-passaged virus, to
       approximately fivefold-lower values. The ability of the envelope
       glycoproteins to complement virus entry roughly correlated with
       sensitivity to neutralization by soluble CD4. Laboratory-adapted viruses
       were sensitive to neutralization by monoclonal antibodies directed
       against the CD4-binding site and the third variable (V3) loop of the
       gp120 glycoprotein. By comparison, viruses with envelope glycoproteins
       from primary patient isolates exhibited decreased sensitivity to
       neutralization by these monoclonal antibodies; for these viruses,
       neutralization sensitivity correlated with replicative ability.
       Subinhibitory concentrations of soluble CD4 and a CD4-binding
       site-directed antibody significantly enhanced the entry of viruses
       containing envelope glycoproteins from some primary patient isolates.
       The sensitivity of viruses containing the different envelope
       glycoproteins to neutralization by soluble CD4 or monoclonal antibodies
       could be predicted by assays dependent on the binding of the inhibitory
       molecule to the oligomeric envelope glycoprotein complex but less well
       by assays measuring binding to the monomeric gp120 glycoprotein. These
       results indicate that the intrinsic structure of the oligomeric envelope
       glycoprotein complex of primary HIV-1 isolates, while often less than
       optimal with respect to the mediation of early events in virus
       replication, allows a relative degree of resistance to neutralizing
       antibodies. The interplay of selective forces for higher virus
       replication efficiency and resistance to neutralizing antibodies could
       explain the temporal course described for the in vivo emergence of HIV-1
       isolates with differing phenotypes.
 DE    Antibodies, Monoclonal/IMMUNOLOGY  Antigens, CD4/PHYSIOLOGY  Binding
       Sites  Cell Line  Human  HIV Envelope Protein gp120/PHYSIOLOGY
       HIV-1/*PHYSIOLOGY  Support, Non-U.S. Gov't  T-Lymphocytes/VIROLOGY
       Viral Envelope Proteins/*PHYSIOLOGY  *Virus Replication  JOURNAL ARTICLE

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

