Synergistic Effect by Combining a gp120-Binding Protein and a gp41-Binding Antibody to Inactivate HIV-1 Virions and Inhibit HIV-1 Infection |
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| Authors: | Xinling Wang Miao Cao Yanling Wu Wei Xu Qian Wang Tianlei Ying Lu Lu Shibo Jiang |
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| Affiliation: | 1.Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; (X.W.); (M.C.); (Y.W.); (W.X.); (Q.W.); (T.Y.);2.Key Laboratory of Reproduction Regulation of National Population and Family Planning Commission, The Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Fudan University, Shanghai 200032, China |
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| Abstract: | ![]()
Acquired immune deficiency syndrome (AIDS) has prevailed over the last 30 years. Although highly active antiretroviral therapy (HAART) has decreased mortality and efficiently controlled the progression of disease, no vaccine or curative drugs have been approved until now. A viral inactivator is expected to inactivate cell-free virions in the absence of target cells. Previously, we identified a gp120-binding protein, mD1.22, which can inactivate laboratory-adapted HIV-1. In this study, we have found that the gp41 N-terminal heptad repeat (NHR)-binding antibody D5 single-chain variable fragment (scFv) alone cannot inactivate HIV-1 at the high concentration tested. However, D5 scFv in the combination could enhance inactivation activity of mD1.22 against divergent HIV-1 strains, including HIV-1 laboratory-adapted strains, primary HIV-1 isolates, T20- and AZT-resistant strains, and LRA-reactivated virions. Combining mD1.22 and D5 scFv exhibited synergistic effect on inhibition of infection by divergent HIV-1 strains. These results suggest good potential to develop the strategy of combining a gp120-binding protein and a gp41-binding antibody for the treatment of HIV-1 infection. |
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| Keywords: | HIV-1 gp120 gp41 antibody combination viral inactivation |
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