title: Recruitment of HIV-1 target cells at topical mucosal sites: a sensitive and early marker for determining the safety of microbicide candidates.
abstract: To explore early biomarkers for establishing more sensitive safety evaluation assays in preclinical settings that determine the potential risks during the application of microbicide candidates, three representative microbicide candidates (cellulose sulphate, nonoxynol-9 and tenofovir), whose safety profiles have been well established in clinical trials, were included to gauge the sensitivities of different assays. Both mouse models and cell lines were employed to determine the sensitivities. The recruitment of immune cells at topical mucosal sites and the upregulation of HIV receptor/coreceptors in vitro were identified as highly sensitive biomarkers of the impact of microbicide candidates. Our data suggest that different evaluations/assays have their inherent sensitivities, and at least one assay from each sensitivity level should be included in the safety evaluation algorithm.
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Ministry of Health, Shanghai Medical College of Fudan University , Shanghai 201508, China.
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Li
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Ministry of Health, Shanghai Medical College of Fudan University , Shanghai 201508, China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Ben
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Ministry of Health, Shanghai Medical College of Fudan University , Shanghai 201508, China.
authors.forename: Songhua
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Ministry of Health, Shanghai Medical College of Fudan University , Shanghai 201508, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Liu
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Ministry of Health, Shanghai Medical College of Fudan University , Shanghai 201508, China.
authors.forename: Huanmei
authors.initials: H
authors.lastname: Wu
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Ministry of Health, Shanghai Medical College of Fudan University , Shanghai 201508, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Ministry of Health, Shanghai Medical College of Fudan University , Shanghai 201508, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
keywords: HIV; coreceptor; microbicides; receptor; recruitment; safety; sensitivity