The effect of deletion of the V3 loop of gp120 on cytotoxic T cell responses and HIV gp120-mediated pathogenesis.
New strategies for improving the efficacy of HIV vaccines are of significant importance. In this study, we analyzed the effect of deletion of the hypervariable V3 loop of gp120 on envelope (env)-specific CTL responses in PBMC of HIV-infected individuals. We showed increased CTL activities against conserved epitopes of the env glycoprotein in cultures induced with the AV3 mutant compared with those stimulated with the full-length env gene products. In contrast to the wild-type env, the AV3 mutant-expressing cells were resistant to Ab-dependent cell-mediated cytotoxicity, formed no syncytia, and neither underwent nor induced apoptosis in CD4+ cells. Thus, the AV3 mutant may redirect immune responses toward conserved epitopes of gp160, has longer expression time due to increased resistance to Ab-dependent cell-mediated cytotoxicity, and does not trigger cytopathic effects associated with apoptosis and syncytium formation. This approach may apply to other Ags of HIV, where deletions of highly variable or immunosuppressive epitopes may improve the efficacy of HIV vaccines.
Kmieciak
D
D
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Wasik
T J
TJ
Teppler
H
H
Pientka
J
J
Hsu
S H
SH
Takahashi
H
H
Okumura
K
K
Kaneko
Y
Y
Kozbor
D
D
D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002461:Cell Line, Transformed; D015686:Gene Products, env / Q000096:biosynthesis / Q000235:genetics; D015726:Giant Cells / Q000276:immunology / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000502:physiology*; D015658:HIV Infections / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016297:Mutagenesis, Site-Directed; D017384:Sequence Deletion; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
D015686:Gene Products, env; D015699:HIV Envelope Protein gp120