Heat-Stable Molecule Derived from Streptococcus cristatus Induces APOBEC3 Expression and Inhibits HIV-1 Replication: e106078

• Published in: PloS one 2014-08, Vol.9 (8)
• Main Authors: Wang, Ziqing, Luo, Yi, Shao, Qiujia, Kinlock, Ballington L, Wang, Chenliang, Hildreth, James EK, Xie, Hua, Liu, Bindong
• Format: Article
• Language: English
• Subjects: Human immunodeficiency virus; Human immunodeficiency virus 1; Streptococcus
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0106078

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.