Antiviral efficacy of Trappin-2/Elafin against Zika virus in the human keratinocyte HaCaT cell line.

Zika virus (ZIKV) is primarily transmitted through mosquito bites, and the skin acts as the initial site of viral entry into the host. Consequently, resident skin cells are among the first targets of infection. The epidermis, mainly composed of keratinocytes, can mount an antiviral response against arboviruses through the production of interferons, interferon-stimulated genes, cytokines, and antimicrobial peptides (AMPs), including the Trappin-2/Elafin (Tr2/E) peptide. However, the antiviral activity of Tr2/E during ZIKV infection remains poorly understood, therefore, this study aimed to investigate the antiviral activity of Tr2/E in human keratinocytes during ZIKV infection. In this study, we evaluated the permissiveness of the human keratinocyte cell line HaCaT to infection with a Mexican isolate of ZIKV and observed that these cells support productive viral infection. We then assessed whether ZIKV infection induces endogenous expression of Tr2/E. Tr2/E transcripts were detected in infected cells and showed increased expression over time post-infection, which correlated with the presence of its corresponding protein. Furthermore, we evaluated the antiviral potential of this peptide through exogenous treatment of infected keratinocytes. A significant reduction in ZIKV infection following Tr2/E treatment was observed. Collectively, these findings provide additional insight into the involvement of AMPs in the antiviral response to ZIKV infection and highlight Tr2/E as a potential antiviral factor.