Male germ cells support long-term propagation of Zika virus

Nature Communications
Christopher L RobinsonShuibing Chen

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.

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Datasets Mentioned

BETA
ABT1487
GSE113177

Methods Mentioned

BETA
reverse transcription PCR
flow cytometry
RNA-seq
biopsy
biopsies
Assay
PCR

Software Mentioned

AbsQuant
FlowJo
Cufflinks
GraphPad Prism
MetaXpress
STAR

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