Abstract
Zika virus (ZIKV) is a newly emerging flavivirus that broadly exhibits in various bodily tissues and fluids, especially in the brain, and ZIKV infection often causes microcephaly. Previous studies have been reported that ZIKV can infect renal cells and can be detected in the urine samples of infected individuals. However, whether ZIKV infection causes renal diseases and its pathogenic mechanisms remains unknown. Here, we identified that ZIKV infection resulted in acute kidney injury (AKI) in both newborn and adult mouse models by increasing the levels of AKI-related biomarkers [e.g., serum creatinine (Scr), kidney injury molecular−1 (Kim-1), and neutrophil gelatinase-associated lipocalin (NGAL)]. ZIKV infection triggered the inflammatory response and renal cell injury by activating Nod-like receptor 3 (NLRP3) inflammasome and secreting interleukin-1β (IL-1β). IL-1β inhibited aquaporins expression and led to water re-absorption disorder. Furthermore, ZIKV infection induced a decreased expression of B-cell lymphoma-2 (Bcl-2) in the kidney. Overexpression of Bcl-2 attenuated ZIKV-induced NLRP3 inflammasome activation in renal cells and down-regulated PARP/caspase-3-mediated renal apoptosis. Overall, our findings demonstrated that ZIKV infection induced AKI by activating NLRP3 inflammasome and apoptosis through suppressing Bcl-2 expression, which provided potential therapeutic targets for ZIKV-associated renal diseases.
Highlights
Zika virus (ZIKV) is a mosquito-borne virus, a member of the Flaviviridae family and ZIKV infection generally causes mild clinical symptoms, such as fever, rash, muscle pain, and conjunctivitis [1]
Our results showed that overexpression of B-cell lymphoma-2 (Bcl-2) extremely decreased IL-18, neutrophil gelatinase-associated lipocalin (NGAL), and kim-1 mRNA expression levels in HK-2 cells infected with ZIKV (Figures 9A–C), indicating the protection role of Bcl-2 on renal cell injury
In vitro studies have shown that ZIKV can infect glomerular cells and renal proximal tubular epithelial cells [9, 10]
Summary
Zika virus (ZIKV) is a mosquito-borne virus, a member of the Flaviviridae family and ZIKV infection generally causes mild clinical symptoms, such as fever, rash, muscle pain, and conjunctivitis [1]. Current epidemic of ZIKV infection has been reported to cause severe diseases, including microcephaly in newborns and Guillain-Barré syndrome in adults [2, 3]. Recent studies on ZIKV pathogenesis have demonstrated that ZIKV exhibits a broad tissue tropism and has the capacity to cause severe diseases [6]. Most clinical studies have demonstrated that high level of ZIKV viral loads can be detected in the urine samples of both adult and infant patients [7, 8]. Cases are reported that two pediatric patients are diagnosed with idiopathic nephrotic syndrome after ZIKV infection and they are in complete remission of the disease after treatment [11, 12]. The pathogenesis and longterm consequences of ZIKV infection in the kidney still need to be studied
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