GSE113177
Male Germ Cells Support Long-Term Propagation of Zika Virus
Evidence of male-to-female sexual transmission of Zika virus (ZIKV) and viral RNA in semen and sperm months after infection support a potential role for testicular cells in ZIKV propagation. Here, we demonstrate that germ cells (GC) are most susceptible to ZIKV. We find that only GC infected by ZIKV, but not those infected by dengue fever (DENV) and yellow fever virus (YFV), produce high levels of infectious virus. This observation coincides with decreased expression of interferon-stimulated gene Ifi44l in ZIKV-infected GC and over-expression of Ifi44l results in reduced ZIKV production. Using primary human testicular tissue, we demonstrate that human GC are also permissive for ZIKV infection and production. Finally, we identify 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. Overall design: RNA-seq was used to compare the gene expression profiles in mock-infected GC with those infected with ZIKV, DENV, and YFV. Among the top 150 most-upregulated genes in DENV- (> 10-fold) or YFV-infected GC (> 4-fold), we selected genes that were upregulated in both DENV- and YFV-infected GC but not in ZIKV-infected GC.