Male germ cells support long-term propagation of Zika virus

Christopher L. Robinson, 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 SeandelShuibing Chen

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number2090
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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