title: Cultivated vaginal microbiomes alter HIV-1 infection and antiretroviral efficacy in colonized epithelial multilayer cultures.
abstract: There is a pressing need for modeling of the symbiotic and at times dysbiotic relationship established between bacterial microbiomes and human mucosal surfaces. In particular clinical studies have indicated that the complex vaginal microbiome (VMB) contributes to the protection against sexually-transmitted pathogens including the life-threatening human immunodeficiency virus (HIV-1). The human microbiome project has substantially increased our understanding of the complex bacterial communities in the vagina however, as is the case for most microbiomes, very few of the community member species have been successfully cultivated in the laboratory limiting the types of studies that can be completed. A genetically controlled ex vivo model system is critically needed to study the complex interactions and associated molecular dialog. We present the first vaginal mucosal culture model that supports colonization by both healthy and dysbiotic VMB from vaginal swabs collected from routine gynecological patients. The immortalized vaginal epithelial cells used in the model and VMB cryopreservation methods provide the opportunity to reproducibly create replicates for lab-based evaluations of this important mucosal/bacterial community interface. The culture system also contains HIV-1 susceptible cells allowing us to study the impact of representative microbiomes on replication. Our results show that our culture system supports stable and reproducible colonization by VMB representing distinct community state types and that the selected representatives have significantly different effects on the replication of HIV-1. Further, we show the utility of the system to predict unwanted alterations in efficacy or bacterial community profiles following topical application of a front line antiretroviral.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pyles
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Vincent
authors.affiliation: Oak Crest Institute of Science, Pasadena, California, United States of America.
authors.forename: Marc M
authors.initials: MM
authors.lastname: Baum
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Barry
authors.initials: B
authors.lastname: Elsom
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Miller
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Carrie
authors.initials: C
authors.lastname: Maxwell
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Tonyia D
authors.initials: TD
authors.lastname: Eaves-Pyles
authors.affiliation: East Tennessee State University, Department of Internal Medicine, Division of Infectious Diseases, Johnson City, Tennessee, United States of America.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Vsevolod L
authors.initials: VL
authors.lastname: Popov
authors.affiliation: Human Pathophysiology and Translational Medicine graduate program, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Nusbaum
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Monique R
authors.initials: MR
authors.lastname: Ferguson
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D018929:Cell Culture Techniques; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology* / Q000821:virology; D005260:Female; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D064307:Microbiota / Q000502:physiology*; D008954:Models, Biological; D009092:Mucous Membrane / Q000187:drug effects / Q000382:microbiology* / Q000821:virology; D014621:Vagina / Q000382:microbiology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D016207:Cytokines