Journal
FRONTIERS IN MICROBIOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2021.825049
Keywords
Zika; herpes; AXL; co-infection; STI; genital
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The study suggests that pre-existing HSV-2 infection may enhance the binding of ZIKV virions to female genital tract epithelial cells, potentially through immune responses. Understanding the mechanisms behind this effect may pave the way for new interventions to disrupt the synergy between herpes and Zika viruses.
Zika virus (ZIKV) is transmitted to people by bite of an infected mosquito and by sexual contact. ZIKV infects primary genital epithelial cells, the same cells targeted by herpes simplex virus 2 (HSV-2). HSV-2 seroprevalence is high in areas where ZIKV is endemic, but it is unknown whether HSV-2 increases the risk for ZIKV infection. Here, we found that pre-infecting female genital tract epithelial cells with HSV-2 leads to enhanced binding of ZIKV virions. This effect did not require active replication by HSV-2, implying that the effect results from the immune response to HSV-2 exposure or to viral genes expressed early in the HSV-2 lifecycle. Treating cells with toll-like receptor-3 ligand poly-I:C also lead to enhanced binding by ZIKV, which was inhibited by the JAK-STAT pathway inhibitor ruxolitinib. Blocking or knocking down the well-studied ZIKV receptor AXL did not prevent binding of ZIKV to epithelial cells, nor prevent enhanced binding in the presence of HSV-2 infection. Blocking the alpha 5 integrin receptor did not prevent ZIKV binding to cells either. Overall, our results indicate that ZIKV binding to genital epithelial cells is not mediated entirely by a canonical receptor, but likely occurs through redundant pathways that may involve lectin receptors and glycosaminoglycans. Our studies may pave the way to new interventions that interrupt the synergism between herpes and Zika viruses.
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