Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus

Abstract

Zika virus (ZIKV) infection is a serious public threat with cases reported in about 70 countries and territories. One of the most serious consequences of ZIKV infection is congenital microcephaly in babies. Congenital microcephaly has been suggested to result from infection of neural progenitor cells (NPCs) in the developing fetal brain. However, the molecular and cellular mechanisms underlying microcephaly development remains to be fully elucidated. In this study, we employed quantitative proteomics to determine protein expression profile that occur during viral replication in NPCs. Bioinformatics analysis of the protein expression changes resulted in the identification of a wide range of cell signaling pathways. Specifically, pathways involved in neurogenesis and embryonic development were markedly altered, along with those associated with cell cycle, apoptosis, lipid metabolism and oxidative stress. Notably, the differential regulation of Ephrin Receptor and PPAR signaling pathways, as revealed by quantitative proteomics and validated by qPCR array, underscores the need to explore these pathways in disease development. Collectively, these results indicate that ZIKV-induced pathogenesis involves complex virus-host reactions; the findings reported here could help shed light on the mechanisms underlying ZIKV-induced microcephaly and ZIKV replication in NPCs.

p‐cymene impairs SARS‐CoV‐2 and Influenza A (H1N1) viral replication: In silico predicted interaction with SARS‐CoV‐2 nucleocapsid protein and H1N1 nucleoprotein

“…Influenza virus strain was studied in MDCK cells in serum‐free MEM, containing 1 μg/ml trypsin TPCK‐treated (Sciex), 2 mM L‐glutamine, 100 U/ml penicillin, and 0.1 mg/ml streptomycin. Evaluation of virus titers and viral growth curves were carried, according to standard protocols 44 . In the present study, we have probed different concentrations of p‐cymene (up to 2 mg/ml).…”

“…Evaluation of virus titers and viral growth curves were carried, according to standard protocols. 44 In the present study, we have probed different concentrations of p-cymene (up to 2 mg/ml).…”

Parsing the Role of PPARs in Macrophage Processes

“…PPARα activation contributes to rapid repair of intestinal epithelium during SIV infection in macaque models ( 54 ). Interestingly, certain viral infections, such as Zika virus, have been shown to modulate and dysregulate PPARα signaling pathways in human cells ( 88 ). The core protein of hepatitis C virus (HCV) was also found to inhibit PPARα expression in humans ( 89 ).…”

PPAR Gamma and Viral Infections of the Brain

“…Notably, PPARγ transcript levels were found to be increased in human NPCs derived from induced pluripotent stem cells (iPSC), as revealed by RNA-seq, along with productive infection, proliferation arrest and apoptosis ( [99], and supplemental data therein). A more recent study used quantitative proteomics and transcriptomics in ZIKV-infected human NPCs and revealed, however, decreased levels of PPARγ mRNA [100]. The same study reported upregulation of RXRγ, of a positive regulator of PPARγ activity (Signal transducer and activator of transcription [STAT] 5 [101]) and of two negative regulators of PPARγ activity (FGR, a member of the Src family of tyrosine protein kinases [102], and the AP-1 transcription factor c-Jun [103]), whereas nuclear receptor coactivator 1 (NCOA1), a coactivator of both RXR and PPARγ [104], was found to be downregulated.…”