Document 0105
 DOCN  M9460105
 TI    Evidence for a functional interaction between the V1/V2 and C4 domains
       of human immunodeficiency virus type 1 envelope glycoprotein gp120.
 DT    9404
 AU    Freed EO; Martin MA; laboratory of Molecular Microbiology, National
       Institute of; Allergy and Infectious Diseases, Bethesda, Maryland 20892.
 SO    J Virol. 1994 Apr;68(4):2503-12. Unique Identifier : AIDSLINE
       MED/94187092
 AB    The domains of the human immunodeficiency virus type 1 (HIV-1) envelope
       glycoprotein that are required for envelope function have been partially
       characterized. Little is known, however, about the nature of the
       interactions between these domains. To identify regions of the HIV-1
       envelope glycoprotein that are involved in interactions necessary for
       proper envelope function, we constructed a series of 14 envelope
       recombinants between the env genes of two HIV-1 isolates. The envelope
       chimeras were examined for their ability to induce syncytia, to be
       proteolytically processed, and to function during a spreading viral
       infection. Our results demonstrate that the exchange between the two
       isolates of the first and second hypervariable regions (V1/V2) of gp120
       results in defects in envelope glycoprotein processing, syncytium
       formation, and infectivity. Long-term passage of cultures infected with
       virus bearing a V1/V2 chimeric envelope glycoprotein leads to the
       emergence of a revertant virus with replication characteristics
       comparable to those of the wild type. Analysis of the revertant
       indicated that an Ile-->Met change in the C4 region of gp120 (between
       hypervariable regions V4 and V5) is responsible for the revertant
       phenotype. This single amino acid change restores infectivity without
       significantly affecting gp160 processing, CD4 binding, or the levels of
       virion-associated gp120. While the Ile-->Met change in C4 greatly
       enhances the fusogenic potential of the V1/V2 chimeric envelope
       glycoprotein, it has a detrimental effect on syncytium formation when
       analyzed in the context of the wild-type envelope. These results suggest
       that an interaction required for proper envelope glycoprotein function
       occurs between the V1/V2 and C4 regions of gp120.
 DE    Antigens, CD4  Base Sequence  Cell Fusion  Chimeric Proteins/PHYSIOLOGY
       Cloning, Molecular  Comparative Study  Human  HIV Envelope Protein
       gp120/*PHYSIOLOGY  HIV Envelope Protein gp41/GENETICS  HIV-1/*GROWTH &
       DEVELOPMENT/PATHOGENICITY  Molecular Sequence Data  Mutagenesis  Protein
       Binding  Protein Processing, Post-Translational  Virulence  JOURNAL
       ARTICLE

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