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 Seandel () and Shuibing Chen ()
Additional contact information
Christopher L. Robinson: Weill Cornell Medical College
Angie C. N. Chong: Weill Cornell Medical College
Alison W. Ashbrook: The Rockefeller University
Ginnie Jeng: Weill Cornell Medical College
Julia Jin: Weill Cornell Medical College
Haiqi Chen: Population Council
Elizabeth I. Tang: Population Council
Laura A. Martin: Weill Cornell Medical College
Rosa S. Kim: Penn State College of Medicine
Reyn M. Kenyon: Weill Cornell Medical College
Eileen Do: Weill Cornell Medical College
Joseph M. Luna: The Rockefeller University
Mohsan Saeed: The Rockefeller University
Lori Zeltser: Columbia University
Harold Ralph: Weill Cornell Medical College-Microscopy and Image Analysis Core Facility
Vanessa L. Dudley: Weill Cornell Medicine–New York Presbyterian Hospital
Marc Goldstein: Weill Cornell Medical College of Cornell University
Charles M. Rice: The Rockefeller University
C. Yan Cheng: Population Council
Marco Seandel: Weill Cornell Medical College
Shuibing Chen: Weill Cornell Medical College

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04444-w

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