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; Shuibing Chen

doi:10.1038/s41467-018-04444-w

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 journal › Article › peer-review

59 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 language	English (US)
Article number	2090
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04444-w
State	Published - Dec 1 2018
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Robinson, C. L., Chong, A. C. N., Ashbrook, A. W., Jeng, G., Jin, J., Chen, H., Tang, E. I., Martin, L. A., Kim, R. S., Kenyon, R. M., Do, E., Luna, J. M., Saeed, M., Zeltser, L., Ralph, H., Dudley, V. L., Goldstein, M., Rice, C. M., Cheng, C. Y., ... Chen, S. (2018). Male germ cells support long-term propagation of Zika virus. Nature communications, 9(1), Article 2090. https://doi.org/10.1038/s41467-018-04444-w

Robinson, CL, Chong, ACN, Ashbrook, AW, Jeng, G, Jin, J, Chen, H, Tang, EI, Martin, LA, Kim, RS, Kenyon, RM, Do, E, Luna, JM, Saeed, M, Zeltser, L, Ralph, H, Dudley, VL, Goldstein, M, Rice, CM, Cheng, CY, Seandel, M & Chen, S 2018, 'Male germ cells support long-term propagation of Zika virus', Nature communications, vol. 9, no. 1, 2090. https://doi.org/10.1038/s41467-018-04444-w

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title = "Male germ cells support long-term propagation of Zika virus",

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.",

author = "Robinson, {Christopher L.} and Chong, {Angie C.N.} and Ashbrook, {Alison W.} and Ginnie Jeng and Julia Jin and Haiqi Chen and Tang, {Elizabeth I.} and Martin, {Laura A.} and Kim, {Rosa S.} and Kenyon, {Reyn M.} and Eileen Do and Luna, {Joseph M.} and Mohsan Saeed and Lori Zeltser and Harold Ralph and Dudley, {Vanessa L.} and Marc Goldstein and Rice, {Charles M.} and Cheng, {C. Yan} and Marco Seandel and Shuibing Chen",

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AU - Robinson, Christopher L.

AU - Chong, Angie C.N.

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AU - Jin, Julia

AU - Chen, Haiqi

AU - Tang, Elizabeth I.

AU - Martin, Laura A.

AU - Kim, Rosa S.

AU - Kenyon, Reyn M.

AU - Do, Eileen

AU - Luna, Joseph M.

AU - Saeed, Mohsan

AU - Zeltser, Lori

AU - Ralph, Harold

AU - Dudley, Vanessa L.

AU - Goldstein, Marc

AU - Rice, Charles M.

AU - Cheng, C. Yan

AU - Seandel, Marco

AU - Chen, Shuibing

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N2 - 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.

AB - 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.

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Male germ cells support long-term propagation of Zika virus

Abstract

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