A complementarity-determining region synthetic peptide acts as a miniantibody and neutralizes human immunodeficiency virus type 1 in vitro.
A complementarity-determining region (CDR) of the mouse monoclonal antibody (mAb) F58 was constructed with specificity to a neutralization-inducing region of human immunodeficiency virus type 1 (HIV-1). The mAb has its major reactivity to the amino acid sequence I--GPGRA in the V3 viral envelope region. All CDRs including several framework amino acids were synthesized from the sequence deduced by cloning and sequencing mAb F58 heavy- and light-chain variable domains. Peptides derived from the third heavy-chain domain (CDR-H3) alone or in combination with the other CDR sequences competed with F58 mAb for the V3 region. The CDR-H3 peptide was chemically modified by cyclization and then inhibited HIV-1 replication as well as syncytium formation by infected cells. Both the homologous IIIB viral strain to which the F58 mAb was induced and the heterologous SF2 strain were inhibited. This synthetic peptide had unexpectedly potent antiviral activity and may be a potential tool for treatment of HIV-infected persons.
Levi
M
M
Department of Virology, National Bacteriological Laboratory, Stockholm, Sweden.
Sällberg
M
M
Rudén
U
U
Herlyn
D
D
Maruyama
H
H
Wigzell
H
H
Marks
J
J
Wahren
B
B
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000235:genetics; D000937:Antigen-Antibody Reactions; D001667:Binding, Competitive; D003001:Cloning, Molecular; D000939:Epitopes; D015483:HIV Antibodies / Q000737:chemistry*; D015497:HIV-1 / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D066298:In Vitro Techniques; D009500:Neutralization Tests; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D014779:Virus Replication
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D007130:Immunoglobulin Idiotypes; D010455:Peptides