Endobiont Viruses Sensed by the Human Host – Beyond Conventional Antiparasitic Therapy

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 co...

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Bibliographic Details
Published in:	PloS one Vol. 7; no. 11; p. e48418
Main Authors:	Fichorova, Raina N., Lee, Yujin, Yamamoto, Hidemi S., Takagi, Yuko, Hayes, Gary R., Goodman, Russell P., Chepa-Lotrea, Xenia, Buck, Olivia R., Murray, Ryan, Kula, Tomasz, Beach, David H., Singh, Bibhuti N., Nibert, Max L.
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 07.11.2012 Public Library of Science (PLoS)
Subjects:	Animals Anti-Bacterial Agents - pharmacology Antibiotics Antiparasitic Agents - pharmacology Antiprotozoan agents Biochemistry Biological response modifiers Biology Birth Cancer Cascades Chemokines Clinical isolates Complications Double-stranded RNA Epithelial cells Female Genitourinary tract Gynecology Health aspects HIV HIV infections Hospitals Host-Pathogen Interactions - drug effects Host-Pathogen Interactions - immunology Human immunodeficiency virus Humans Immunity, Innate - drug effects Immunology Infection Infections Inflammation Inflammation - pathology Interferon Interferon Regulatory Factor-3 - metabolism Laboratories Leishmania Medical schools Medicine Metronidazole Metronidazole - pharmacology Models, Biological Molecular biology Obstetrics Papillomavirus infections Parasites Parasites - drug effects Parasites - virology Parasitic diseases Pregnancy Pregnancy complications Premature birth Premature infants Protozoa Ribonuclease III - metabolism Risk factors RNA, Double-Stranded - metabolism Sexually transmitted diseases Signal Transduction - drug effects Signal Transduction - immunology STD Symbiosis - drug effects TLR3 protein Toll-Like Receptor 3 - metabolism Toll-like receptors Totiviridae - drug effects Trichomonas vaginalis Trichomonas vaginalis - drug effects Trichomonas vaginalis - isolation & purification Trichomonas vaginalis - pathogenicity Trichomonas vaginalis - virology Trichomoniasis Vagina - immunology Vagina - parasitology Vagina - pathology Vagina - virology Viral infections Virion - drug effects Virus Diseases - immunology Virus Diseases - pathology Viruses Womens health New York United States > US Massachusetts
ISSN:	1932-6203, 1932-6203
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Current address: Xenia Chepa-Lotrea: NIH, NIDDK, Liver Disease Branch Immunology, Section, Bethesda, Maryland, United States of America Current address: Northeastern University, Boston, Massachusetts, United States of America Current address: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America Performed the experiments: RNF YL HSY ORB XCL. Analyzed the data: RNF YL HSY RM ORB. Wrote the paper: RNF. Conceived and designed the experiments, immunology and cell biology: RNF; virology: MLN. Contributed reagents/materials/analysis tools, LPS and primary TV isolates: BNS DHB GH; virion isolation and RT-PCR: YT TK RPG; TVV dsRNA and RNAse treatments: YT; TV culture: DHB GH XCL RM ORB RNF; TV cloning: RNF; Western blot: ORB; qNPA: HSY; luciferase and immunoassays: YL HSY RM ORB. Reviewed and approved the manuscript: RNF YL HSY YT GH RPG XCL ORB RM TK DHB BNS MLN. Recruited clinical subjects: BNS.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0048418