Zika virus infects renal proximal tubular epithelial cells with prolonged persistency and cytopathic effects

Abstract

Zika virus (ZIKV) infection can cause fetal developmental abnormalities and Guillain–Barré syndrome in adults. Although progress has been made in understanding the link between ZIKV infection and microcephaly, the pathology of ZIKV, particularly the viral reservoirs in human, remains poorly understood. Several studies have shown that compared to serum samples, patients’ urine samples often have a longer duration of ZIKV persistency and higher viral load. This finding suggests that an independent viral reservoir may exist in the human urinary system. Despite the clinical observations, the host cells of ZIKV in the human urinary system are poorly characterized. In this study, we demonstrate that ZIKV can infect renal proximal tubular epithelial cells (RPTEpiCs) in immunodeficient mice in vivo and in both immortalized and primary human renal proximal tubular epithelial cells (hRPTEpiCs) in vitro. Importantly, ZIKV infection in mouse kidneys caused caspase-3-mediated apoptosis of renal cells. Similarly, in vitro infection of immortalized and primary hRPTEpiCs resulted in notable cytopathic effects. Consistent with the clinical observations, we found that ZIKV infection can persist with prolonged duration in hRPTEpiCs. RNA-Seq analyses of infected hRPTEpiCs revealed a large number of transcriptional changes in response to ZIKV infection, including type I interferon signaling genes and anti-viral response genes. Our results suggest that hRPTEpiCs are a potential reservoir of ZIKV in the human urinary system, providing a possible explanation for the prolonged persistency of ZIKV in patients’ urine.

Emerging Microbes & Infections (2017) 6, e77; doi:10.1038/emi.2017.67; published online 23 August 2017

• cytopathic effects
• prolonged persistency
• renal proximal tubular epithelial cells
• urinary system
• Zika virus

Acknowledgments

This work was supported by the Natural Science Foundation of China (81430030), ShanghaiTech University (Startup Fund to BJ and JL), National Basic Research Program of China (2014CB542502), Shanghai ShenKang Hospital Development Center (SHDC12014104), Shanghai Public Health Clinical Center (2016-28 ksf0730), and the Technology Service Platform for Detecting High level Biological Safety Pathogenic Microorganism (15DZ2290200, Shanghai Science and Technology Commission).

Supplementary Information for this article can be found on the Emerging Microbes & Infections website (http://www.nature.com/emi)