Heat-Stable Molecule Derived from Streptococcus cristatus Induces APOBEC3 Expression and Inhibits HIV-1 Replication |
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Authors: | Ziqing Wang Yi Luo Qiujia Shao Ballington L Kinlock Chenliang Wang James E K Hildreth Hua Xie Bindong Liu |
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Institution: | 1. Center for AIDS Health Disparities Research, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.; 2. Department of Oral Biology and Research, School of Dentistry, Meharry Medical College, Nashville, Tennessee, United States of America.; 3. Institute of Gastroenterology and Institute of Human Virology, Sun Yat-sen University, Guangzhou, Guangdong, Peoples of Republic of China.; University Hospital Zurich, Switzerland, |
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Abstract: | Although most human immunodeficiency virus type 1 (HIV-1) cases worldwide are transmitted through mucosal surfaces, transmission through the oral mucosal surface is a rare event. More than 700 bacterial species have been detected in the oral cavity. Despite great efforts to discover oral inhibitors of HIV, little information is available concerning the anti-HIV activity of oral bacterial components. Here we show that a molecule from an oral commensal bacterium, Streptococcus cristatus CC5A can induce expression of APOBEC3G (A3G) and APOBEC3F (A3F) and inhibit HIV-1 replication in THP-1 cells. We show by qRT-PCR that expression levels of A3G and A3F increase in a dose-dependent manner in the presence of a CC5A extract, as does A3G protein levels by Western blot assay. In addition, when the human monocytic cell line THP-1 was treated with CC5A extract, the replication of HIV-1 IIIB was significantly suppressed compared with IIIB replication in untreated THP-1 cells. Knock down of A3G expression in THP-1 cells compromised the ability of CC5A to inhibit HIV-1 IIIB infectivity. Furthermore, SupT1 cells infected with virus produced from CC5A extract-treated THP-1 cells replicated virus with a higher G to A hypermutation rate (a known consequence of A3G activity) than virus used from untreated THP-1 cells. This suggests that S. cristatus CC5A contains a molecule that induces A3G/F expression and thereby inhibits HIV replication. These findings might lead to the discovery of a novel anti-HIV/AIDS therapeutic. |
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