Myeloid C-type lectin 5A (CLEC5A) is critical for ZIKV-induced orchitis and epididymitis
Chun-Hong Chen1, Shie-Liang Hsieh2 National Institute of Infectious Diseases and Vaccinology NHRI1, Genomics Research Center, Academia Sinica2
ZIKA virus (ZIKV) is a member of the Flaviviridae family, and has become an international public crisis due to global spreading by Aedes aegypti and Aedes albopictus. Unlike other members of flaviviruses, ZIKV prefers to infect genital organs and cause abortion and infertility of victims. ZIKV can survive in semen for a couple of months and causes severe orchitis, the underlying mechanism is still unclear. We found that CLEC5A, the pattern recognition receptor to dengue virus and Japanese encephalitis virus, also recognize ZIKV, and plays a critical role in ZIKV-induced orchitis and epididymitis. We are surprised to find that CLEC5A is highly expressed in tissue macrophages in male genital organs, and inflammation in testis and epididymis is attenuated dramatically with increase of sperm number and activity were observed in Stat1-/- Clec5A-/- mice than in Stat1-/- mice. Notably, the sperm number and activity in ZIKV-infected Stat1-/- Clec5A-/- mice is similar to un-infected Stat1-/- mice. All these observations suggest that CLEC5A plays a key role in ZIKV-induced inflammatory reactions, and blockade of CLEC5A may become a novel approach to prevent infertily in ZIKV-infected patients in the future.
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