Ebselen alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission.
Yogy SimanjuntakJian-Jong LiangSi-Yu ChenJin-Kun LiYi-Ling LeeHan-Chung WuYi-Ling LinPublished in: PLoS pathogens (2018)
Despite the low case fatality, Zika virus (ZIKV) infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Antiviral and vaccine developments against ZIKV are still ongoing; therefore, in the meantime, preventing the disease transmission is critical. Primarily transmitted by Aedes species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice lacking interferon-α/β and -γ receptors to study the testicular pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively damaged mouse testes, increased testicular oxidative stress as indicated by the levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4, spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines including IL-1β, IL-6, and G-CSF. We then evaluated the potential role of the antioxidant ebselen (EBS) in alleviating the testicular pathology with ZIKV infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is currently in clinical trials for various diseases. ZIKV infection could be on the list for potential use of EBS, for alleviating the testicular pathogenesis with ZIKV infection and preventing its sexual transmission.
Keyphrases
- zika virus
- dengue virus
- aedes aegypti
- germ cell
- oxidative stress
- nitric oxide
- inflammatory response
- clinical trial
- mental health
- diabetic rats
- anti inflammatory
- type diabetes
- metabolic syndrome
- mouse model
- skeletal muscle
- endoplasmic reticulum stress
- induced apoptosis
- quantum dots
- ischemia reperfusion injury
- high glucose
- open label
- nitric oxide synthase
- study protocol
- signaling pathway
- stress induced
- double blind