Document 0589
 DOCN  M9550589
 TI    Spontaneous reversion of human immunodeficiency virus type 1
       neutralization-resistant variant HXB2thr582: in vitro selection against
       cytopathicity highlights gp120-gp41 interactive regions.
 DT    9505
 AU    Stern TL; Reitz MS Jr; Robert-Guroff M; Laboratory of Tumor Cell
       Biology, National Cancer Institute,; National Institutes of Health,
       Bethesda, MD 20892-4255.
 SO    J Virol. 1995 Mar;69(3):1860-7. Unique Identifier : AIDSLINE
       MED/95156619
 AB    Spontaneous revertants of the immune-selected variant HXB2thr582, which
       resists neutralization by certain conformationally dependent antibodies
       specific for the CD4-binding site on gp120 (such as F105), appeared
       after long-term culture in the absence of immune-selecting serum.
       Molecular analysis showed some of the viruses in the revertant stock
       contained a simple back mutation, whereas others retained the Thr-582
       codon but contained a substitution of serine for phenylalanine in gp41
       at position 673. Neutralization sensitivity to the selecting serum and
       to F105 of infectious clones containing either the back mutation or the
       compensatory mutation, HXB2thr582ser673, was confirmed.
       HXB2thr582-infected cells have a greater propensity for syncytium
       formation and single cell killing than do either the parental HXB2 or
       the revertant HXB2thr582ser673. This suggests that the revertant arose
       by selection in vitro for a less cytopathic virus. Our results link
       three envelope regions shown to influence virus-cell fusion as well as
       neutralization by antibody: the CD4-binding region, the leucine zipper
       domain, and a region hidden to antipeptide antibodies upon envelope
       oligomerization. Taken together they illustrate the functional
       importance of the gp120-gp41 interaction and emphasize the impact of the
       interplay between envelope regions on overall conformation and function
       and on recognition by neutralizing antibodies.
 DE    Amino Acid Sequence  Base Sequence  Cells, Cultured  Clone Cells
       Cytopathogenic Effect, Viral  DNA, Viral/GENETICS  Human  HIV
       Antibodies/IMMUNOLOGY  HIV Antigens/*GENETICS  HIV Envelope Protein
       gp120/*METABOLISM  HIV Envelope Protein gp41/*METABOLISM
       HIV-1/GENETICS/*IMMUNOLOGY  In Vitro  Molecular Sequence Data  Mutation
       Neutralization Tests  Protein Binding  JOURNAL ARTICLE

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