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

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.

Zika Virus Infection of Sertoli Cells Alters Protein Expression Involved in Activated Immune and Antiviral Response Pathways, Carbohydrate Metabolism and Cardiovascular Disease

“…Dengue virus (DENV), another relative of ZIKV, depends on the glycolysis pathways for its replication [62]. High concentrations of glucose can restrict the growth of ZIKV in human kidney cells [63]. ZIKV infection increases glucose incorporation into the TCA cycle in mosquito cells, but the mechanism is not clear [64].…”

Zika Virus Induces Sex-Dependent Metabolic Changes in Drosophila melanogaster to Promote Viral Replication

“…Infected Dicer-2 male flies also show a significant decrease in glycogen levels despite the lack of change in the other carbohydrates. Noticeably, Dengue virus (DENV), which is closely related to ZIKV, depends on the glycolysis pathway for its replication ( 45 ), and high glucose levels have been shown to restrict ZIKV infection in human kidney cells ( 46 ). In line with our findings, recent studies in human cells also report dramatic changes in carbohydrate concentrations after ZIKV infection ( 47 ).…”

High Glucose Induces in HK2 Kidney Cells an IFN–Dependent ZIKV Antiviral Status Fueled by Viperin

“…In prior experiments, cells were adapted to high glucose (25 mM) for a 10-day period to allow metabolic reprogramming. Glucose concentrations were chosen based on our recent study [ 23 ] and on previous published works [ 26 , 27 , 28 , 29 ]. The number of cells seeded in the two conditions was adjusted based on the cell growth kinetics study to avoid the multiplicity of infection (MOI) bias during infections (as previously described in [ 23 ]).…”

“…Glucose concentrations were chosen based on our recent study [ 23 ] and on previous published works [ 26 , 27 , 28 , 29 ]. The number of cells seeded in the two conditions was adjusted based on the cell growth kinetics study to avoid the multiplicity of infection (MOI) bias during infections (as previously described in [ 23 ]). A549 cells (Invivogen Inc, Toulouse, France) were grown in DMEM medium supplemented with 10% heat-inactivated FBS, non-essential amino acids, 10 µg.mL −1 blasticidin and 100 mg.mL −1 zeocin (InvivoGen, Toulouse, France).…”

“…Our recent study aimed to improve our knowledge on ZIKV replication in human HK-2 kidney cells under high glucose concentration (HK-2 HGC ) compared to the HK-2 cells under normal glucose condition (HK-2 NGC ) [ 23 ]. We reported, for the first time, that an elevated glucose level can inhibit ZIKV infection in HK-2 cells by directly acting on the replication step without affecting early infection stages.…”