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Endobiont viruses sensed by the human host - beyond conventional antiparasitic therapy.

Raina N Fichorova | Yujin Lee | Hidemi S Yamamoto | Yuko Takagi | Gary R Hayes | Russell P Goodman | Xenia Chepa-Lotrea | Olivia R Buck | Ryan Murray | Tomasz Kula | David H Beach | Bibhuti N Singh | Max L Nibert
PloS one | 2012

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.

Pubmed ID: 23144878

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI079085
  • Agency: NIAID NIH HHS, United States
    Id: 5R01AI079085-03
  • Agency: NIAID NIH HHS, United States
    Id: R56 AI091889
  • Agency: NIAID NIH HHS, United States
    Id: 1R56AI091889-01A1
  • Agency: NCRR NIH HHS, United States
    Id: 5UL1RR025758-02
  • Agency: NIAID NIH HHS, United States
    Id: RC1 AI086788
  • Agency: NCRR NIH HHS, United States
    Id: UL1 RR025758

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Charles River Laboratories (tool)

RRID:SCR_003792

Commercial organism provider selling mice, rats and other model animals. American corporation specializing in a variety of pre-clinical and clinical laboratory services for the pharmaceutical, medical device and biotechnology industries. It also supplies assorted biomedical products and research and development outsourcing services for use in the pharmaceutical industry. (Wikipedia)

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HEK293 (tool)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

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