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The Effect of Deletion of the V3 Loop of gp120 on Cytotoxic T Cell Responses and HIV gp120-Mediated Pathogenesis¹

Dariusz Kmieciak^2,3,*, Thomas J. Wasik^2,*, Hedy Teppler^4,, Janet Pientka^4,, Susan H. Hsu, Hidemi Takahashi^§, Ko Okumura^¶, Yutaro Kaneko^|| and Danuta Kozbor^2,5,*

Departments of ^* Microbiology and Immunology and Medicine, Division of Infectious Diseases, Thomas Jefferson University, Philadelphia, PA 19107; The Histocompatibility Laboratory, American Red Cross, Philadelphia, PA 19123; ^§ Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan; ^¶ Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan; and ^|| Ajinomoto Co., Inc., Kyobashi, Tokyo, Japan

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 V3 mutant compared with those stimulated with the full-length env gene products. In contrast to the wild-type env, the V3 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 V3 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.

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