title: Endobiont viruses sensed by the human host - beyond conventional antiparasitic therapy.
abstract: Wide-spread protozoan parasites carry endosymbiotic dsRNA viruses with uncharted implications to the human host. Among them, Trichomonas vaginalis, a parasite adapted to the human genitourinary tract, infects globally ∼250 million each year rendering them more susceptible to devastating pregnancy complications (especially preterm birth), HIV infection and HPV-related cancer. While first-line antibiotic treatment (metronidazole) commonly kills the protozoan pathogen, it fails to improve reproductive outcome. We show that endosymbiotic Trichomonasvirus, highly prevalent in T. vaginalis clinical isolates, is sensed by the human epithelial cells via Toll-like receptor 3, triggering Interferon Regulating Factor -3, interferon type I and proinflammatory cascades previously implicated in preterm birth and HIV-1 susceptibility. Metronidazole treatment amplified these proinflammatory responses. Thus, a new paradigm targeting the protozoan viruses along with the protozoan host may prevent trichomoniasis-attributable inflammatory sequelae.
authors.affiliation: Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. rfichorova@rics.bwh.harvard.edu
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.forename: Yujin
authors.initials: Y
authors.lastname: Lee
authors.forename: Hidemi S
authors.initials: HS
authors.lastname: Yamamoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takagi
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hayes
authors.forename: Russell P
authors.initials: RP
authors.lastname: Goodman
authors.forename: Xenia
authors.initials: X
authors.lastname: Chepa-Lotrea
authors.forename: Olivia R
authors.initials: OR
authors.lastname: Buck
authors.forename: Ryan
authors.initials: R
authors.lastname: Murray
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kula
authors.forename: David H
authors.initials: DH
authors.lastname: Beach
authors.forename: Bibhuti N
authors.initials: BN
authors.lastname: Singh
authors.forename: Max L
authors.initials: ML
authors.lastname: Nibert
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000977:Antiparasitic Agents / Q000494:pharmacology*; D005260:Female; D054884:Host-Pathogen Interactions / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D008795:Metronidazole / Q000494:pharmacology; D008954:Models, Biological; D010271:Parasites / Q000187:drug effects* / Q000821:virology*; D012330:RNA, Double-Stranded / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013559:Symbiosis / Q000187:drug effects*; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D019196:Totiviridae / Q000187:drug effects*; D014246:Trichomonas vaginalis / Q000187:drug effects / Q000302:isolation & purification / Q000472:pathogenicity / Q000821:virology; D014621:Vagina / Q000276:immunology / Q000469:parasitology / Q000473:pathology / Q000821:virology; D014771:Virion / Q000187:drug effects; D014777:Virus Diseases / Q000276:immunology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D000977:Antiparasitic Agents; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D012330:RNA, Double-Stranded; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D008795:Metronidazole; D043244:Ribonuclease III