Journal Article

Ebselen alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission

Chen, Si-Yu, Wu, Han-Chung, Liang, Jian-Jong, Simanjuntak, Yogy, Lin, Yi-Ling, Lee, Yi-Ling, Li, Jin-Kun

2018

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aedes / Animals / Anti-Inflammatory Agents, Non-Steroidal - therapeutic use / Antioxidants / Antioxidants - therapeutic use / Aquatic insects / Azoles - therapeutic use / Biology and Life Sciences / Cell Nucleus Shape - drug effects / Cell Nucleus Size - drug effects / Cell Shape - drug effects / Cell Size - drug effects / Clinical trials / Cytokines / Cytokines - metabolism / Disease / Disease transmission / Enzymes / Fatalities / Flavivirus / Glutathione / Glutathione peroxidase / Granulocyte colony-stimulating factor / Guillain-Barre syndrome / Homology / Infants / Infections / Infiltration / Inflammation / Inflammatory response / Interferon / Interleukin 1 / Interleukin 6 / Isoindoles / Leukocytes - drug effects / Leukocytes - immunology / Leukocytes - metabolism / Leukocytes - pathology / Male / Medical research / Medicine and Health Sciences / Mice / Mice, Inbred C57BL / Mice, Knockout / Mice, Transgenic / Microcephaly / Microencephaly / Mosquitoes / Nitric oxide / Organoselenium Compounds - therapeutic use / Oxidative stress / Oxidative Stress - drug effects / Pathogenesis / Pathology / Peroxidase / Prevention / Reactive oxygen species / Receptors / Receptors, Interferon - genetics / Receptors, Interferon - metabolism / Research and Analysis Methods / Rodents / Sexual transmission / Sexually transmitted diseases / Sexually Transmitted Diseases, Viral - drug therapy / Sexually Transmitted Diseases, Viral - pathology / Sexually Transmitted Diseases, Viral - transmission / Sexually Transmitted Diseases, Viral - virology / Sperm / Spermatogenesis / Spermatogenesis - drug effects / Spermatozoa - immunology / Spermatozoa - metabolism / Spermatozoa - pathology / Spermatozoa - virology / Studies / Testes / Testis - drug effects / Testis - immunology / Testis - pathology / Testis - virology / Vaccine development / Vector-borne diseases / Viruses / Zika virus / Zika Virus - drug effects / Zika Virus - immunology / Zika Virus - pathogenicity / Zika Virus Infection - drug therapy / Zika Virus Infection - pathology / Zika Virus Infection - transmission / Zika Virus Infection - virology / α-Interferon / β-Interferon / γ-Interferon