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M94A3334.TXT
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1994-10-25
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Document 3334
DOCN M94A3334
TI Domain between V1 and V2 regions of HIV-1 gp120 is critical for virus
infectivity.
DT 9412
AU Wang WK; Essex M; Lee TH; Department of Cancer Biology, Harvard School
of Public Health,; Boston, MA 02115.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):10 (abstract no. 014A). Unique
Identifier : AIDSLINE ICA10/94369241
AB OBJECTIVE: Between the first and second variable regions (V1 and V2) of
HIV-1 gp120 is a conserved domain containing a relatively large number
of charged residues. These residues were investigated for their role in
viral infectivity. METHODS: Mutant proviruses each with an alanine
substituted for one of 9 highly conserved charged residues in the domain
between V1 and V2 of HIV-1 gp120 were generated by site-directed
mutagenesis. Virus infectivity was monitored by reverse transcriptase.
Envelope expression, processing and incorporation into virions were
examined by western blot. A one-round complementation chloramphenicol
acetyltransferase (CAT) assay was performed to study early steps of
virus replication. RESULTS: Six of 9 mutant viruses had growth kinetics
comparable to that of the wild type. Two mutant viruses showed a slight
delay and one mutant with a substitution at position 180 had severely
impaired infectivity. Additional substitutions at this position with
residues of the same charge, opposite charge or no charge resulted in
severely impaired infectivity. This impairment could not be attributed
to global changes in gp120 conformation because expression and
incorporation of envelope proteins into virions and recognition of
mutants by conformation-dependent monoclonal antibodies were not
affected. In a one-round replication assay, mutant virus with an alanine
at position 180 had significantly reduced CAT activity. CONCLUSIONS: The
domain flanked by V1 and V2 of gp120 is functionally involved in virus
infectivity. Of the charged residues in this domain, aspartic acid at
position 180 is most critical for early steps of virus replication.
Previously, anti-V2 monoclonal antibodies that mapped to a region
overlapping with residue 180 could block virus infectivity. Since this
aspartic residue is conserved by all classes of HIV-1, it may be a
potential target for future anti-viral designs.
DE Aspartic Acid/METABOLISM Blotting, Western Chloramphenicol
Acetyltransferase/ANALYSIS HIV Envelope Protein
gp120/ANALYSIS/*GENETICS HIV-1/*GENETICS/METABOLISM/PATHOGENICITY
Mutagenesis, Site-Directed MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).