Emerging clinical evidence has linked Dengue (DENV) and Zika (ZIKV) virus infections with the development of a range of eye diseases. Although, in vivo and in vitro experiments have shown that ZIKV, and from our recent work also DENV, are able to infect the retina and eye-derived cells, the mechanisms of virus induced effects in the eye remain poorly understood.
The goals of the current study were to compare DENV and ZIKV infections in the eye and to explore the host cell responses. Human retinal pigment epithelium (RPE), retinal endothelium (RE) and Muller cells (MC) were challenged with either DENV or ZIKV and the expression of viral and host defence related genes was evaluated by RT-PCR. Infected cells and the expression of cellular receptors were measured by immunofluorescence and flow cytometry.
Both viruses infected RPE, RE and Muller cells but remarkably, all cells showed higher susceptibility to ZIKV than DENV. In addition, RPE and Muller cells were more permissive to infection and these 3 cell types showed differential activation of interferon stimulated genes (ISGs). Further, the susceptibility to infection did not correlate with the level of the proposed ZIKV receptors Axl and Mertk. Despite lower infectivity, DENV was more effective in inducing TNFa and IL6 in RPE and RE cells. Consistent with in vitro data, ZIKV demonstrated a higher tropism to infect the eye of 1 day old immunocompetent mice than DENV.
Our results provide evidence demonstrating that although both ZIKV and DENV can infect the eye there are substantial differences in cell tropism and host responses that could explain the clinically observed eye diseases.