Male Germ Cells Support Long-Term Propagation of Zika Virus
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ABSTRACT:
PROVIDER: PRJNA450377 | ENA |
REPOSITORIES: ENA
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Project description: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.
2018-06-06 | GSE113177 | GEO
Project description: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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Project description:This study aims to study binding events between the Zika virus RNA genome and endogenous transcripts during infection of a human cell line. We develop a novel psolaren-based cross-linking technique to preserve interactions between mRNA and the Zika genome. Interacting RNA molecules are ligated together prior to reversal of the cross-links and selection for Zika-containing fragments. Reverse transcription and paired-end high-throughput sequencing then allow us to identify the interacting transcripts. We generated three batches of libraries, where all samples in each batch were generated from the same pool of RNA. Within each batch, we have the livefire sample, where the protocol was performed as described above; a reverse-control sample, where the protocol was performed by reversing the cross-links prior to ligation; and a no-cross-link control, where the protocol was performed without any cross-linking. The latter two samples represent negative controls where no genuine interactions should be observed.
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