Male germ cells support long-term propagation of Zika virus

• Published in: Nature communications Vol. 9; no. 1; pp. 2090 - 11
• Main Authors: Robinson, Christopher L., Chong, Angie C. N., Ashbrook, Alison W., Jeng, Ginnie, Jin, Julia, Chen, Haiqi, Tang, Elizabeth I., Martin, Laura A., Kim, Rosa S., Kenyon, Reyn M., Do, Eileen, Luna, Joseph M., Saeed, Mohsan, Zeltser, Lori, Ralph, Harold, Dudley, Vanessa L., Goldstein, Marc, Rice, Charles M., Cheng, C. Yan, Seandel, Marco, Chen, Shuibing
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.05.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/100; 13/106; 38/91; 631/154; 631/326/596/2557; 631/326/596/2564; 692/698/690/1520; Animals; Antigens - biosynthesis; Antiviral Agents - pharmacology; Berberine; Berberine - pharmacology; Cell Proliferation; Cells, Cultured; Cercopithecus aethiops; Cytoskeletal Proteins - biosynthesis; Dengue fever; Dengue Virus - growth & development; Disease transmission; Fever; Gene expression; Germ cells; Humanities and Social Sciences; Humans; Infections; Interferon; Interferon Type I - immunology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Propagation; Receptor, Interferon alpha-beta - genetics; Ribonucleic acid; RNA; RNA viruses; RNA, Viral - analysis; RNA, Viral - isolation & purification; Science; Science (multidisciplinary); Semen; Sexual transmission; Sexually Transmitted Diseases, Viral - prevention & control; Sexually Transmitted Diseases, Viral - virology; Spermatozoa - virology; Testes; Testis - cytology; Testis - virology; Vector-borne diseases; Vero Cells; Viral diseases; Virus Replication - drug effects; Virus Replication - physiology; Viruses; Yellow fever virus - growth & development; Zika virus; Zika Virus - growth & development; Zika Virus - isolation & purification; Zika Virus Infection - transmission; Zika Virus Infection - virology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04444-w

Evidence 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. Zika virus (ZIKV) can persist for months in semen and sperm. Here, the authors show that germ cells, compared to other cell types in the reproductive tract, are most susceptible to ZIKV and produce high levels of progeny virus, which coincides with decreased expression of the interferon-stimulated gene Ifi44l .