Male germ cells support long-term propagation of Zika virus

• DOI: 10.1038/s41467-018-04444-w
• Publication Date: 2018-05-22T09:01:06Z
• Authors: Christopher L. Ro...; Angie C. N. Chong; Alison W. Ashbrook; Ginnie Jeng; Julia Jin; Haiqi Chen; Elizabeth I. Tang; Laura A. Martin; Rosa S. Kim; Reyn M. Kenyon; Eileen Do; Joseph M. Luna; Mohsan Saeed; Lori Zeltser; Harold Ralph; Vanessa L. Dudley; Marc Goldstein; Charles M. Rice; C. Yan Cheng; Marco Seandel; Shuibing Chen
• Keywords: Male; 0301 basic medicine; Berberine; Science; Receptor, Interferon alpha-beta; Antiviral Agents; Article; Mice; 03 medical and health sciences; Chlorocebus aethiops; Testis; Animals; Humans; Antigens; Cells, Cultured; Cell Proliferation; Mice, Knockout; Q; Sexually Transmitted Diseases, Viral; Dengue Virus; Spermatozoa; 3. Good health; Mice, Inbred C57BL; Cytoskeletal Proteins; Interferon Type I; RNA, Viral

AbstractEvidence of male-to-female sexual transmission of Zika virus (ZIKV) and viral RNA in semen and sperm months after infection supports a potential role for testicular cells in ZIKV propagation. Here, we demonstrate that germ cells (GCs) are most susceptible to ZIKV. We found that only GCs infected by ZIKV, but not those infected by dengue virus and yellow fever virus, produce high levels of infectious virus. This observation coincides with decreased expression of interferon-stimulated gene Ifi44l in ZIKV-infected GCs, and overexpression of Ifi44l results in reduced ZIKV production. Using primary human testicular tissue, we demonstrate that human GCs are also permissive for ZIKV infection and production. Finally, we identified berberine chloride as a potent inhibitor of ZIKV infection in both murine and human testes. Together, these studies identify a potential cellular source for propagation of ZIKV in testes and a candidate drug for preventing sexual transmission of ZIKV.