Zika Virus Growth in Human Kidney Cells Is Restricted by an Elevated Glucose Level.

Alawiya Reslan,Liadrine Moukendza Koundi,Jean-Loup Bascands,Gilles Gadea,Juliano G. Haddad,Philippe Desprès

doi:10.3390/ijms22052495

Abstract

Mosquito-borne Zika virus (ZIKV) became a real threat to human health due to the lack of vaccine and effective antiviral treatment. The virus has recently been responsible for a global outbreak leading to millions of infected cases. ZIKV complications were highlighted in adults with Guillain–Barré syndrome and in newborns with increasing numbers of congenital disorders ranging from mild developmental delays to fatal conditions. The ability of ZIKV to establish a long-term infection in diverse organs including the kidneys has been recently documented but the consequences of such a viral infection are still debated. Our study aimed to determine whether the efficiency of ZIKV growth in kidney cells relates to glucose concentration. Human kidney HK-2 cells were infected with different ZIKV strains in presence of normal and high glucose concentrations. Virological assays showed a decrease in viral replication without modifying entry steps (viral binding, internalization, fusion) under high glucose conditions. This decrease replication was associated with a lower virus progeny and increased cell viability when compared to ZIKV-infected HK-2 cells in normal glucose concentration. In conclusion, we showed for the first time that an elevated glucose level influences ZIKV replication level with an effect on kidney cell survival.

Highlights

Mosquito-borne Zika virus (ZIKV) belonging to the flavivirus genus (Flaviviridae family), was first isolated in 1947 from a sentinel monkey in the Zika forest (Uganda)
To eliminate a potential role for osmolarity in the observed phenomenon, HK-2 cells were adapted with mannitol as it was done for glucose
Several clinical studies have identified diabetes as a risk factor, no experimental study has ever reported if a hyperglycemic environment could influence flavivirus replication

Summary

Introduction

Mosquito-borne Zika virus (ZIKV) belonging to the flavivirus genus (Flaviviridae family), was first isolated in 1947 from a sentinel monkey in the Zika forest (Uganda). In 2007, the first ZIKV outbreak was reported on Yap Island, affecting 70% of inhabitants [1]. From this date, ZIKV spread to the Pacific Islands, and South and Central America, and became a major health concern worldwide [2]. Supporting evidence depicts ZIKV’s ability to disseminate from human to human, through non-vectorial routes [6,7,8]. These new behaviors highlight ZIKV enlarged cellular tropism as well as a long-term viral infection in target tissues

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