title: Heat-stable molecule derived from Streptococcus cristatus induces APOBEC3 expression and inhibits HIV-1 replication.
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.
authors.affiliation: Center for AIDS Health Disparities Research, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for AIDS Health Disparities Research, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Center for AIDS Health Disparities Research, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.
authors.forename: Qiujia
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Center for AIDS Health Disparities Research, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.
authors.forename: Ballington L
authors.initials: BL
authors.lastname: Kinlock
authors.affiliation: Center for AIDS Health Disparities Research, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America; Institute of Gastroenterology and Institute of Human Virology, Sun Yat-sen University, Guangzhou, Guangdong, Peoples of Republic of China.
authors.forename: Chenliang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Center for AIDS Health Disparities Research, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.
authors.forename: James E K
authors.initials: JE
authors.lastname: Hildreth
authors.affiliation: Department of Oral Biology and Research, School of Dentistry, Meharry Medical College, Nashville, Tennessee, United States of America.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.affiliation: Center for AIDS Health Disparities Research, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.
authors.forename: Bindong
authors.initials: B
authors.lastname: Liu
mesh_terms: D000071480:APOBEC-3G Deaminase; D018829:Adhesins, Bacterial / Q000737:chemistry / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000378:metabolism*; D010450:Endopeptidases / Q000737:chemistry / Q000494:pharmacology*; D004795:Enzyme Stability; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D013291:Streptococcus / Q000145:classification / Q000201:enzymology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D018829:Adhesins, Bacterial; D019380:Anti-HIV Agents; D010450:Endopeptidases; C053088:C5a peptidase; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase