Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells
Document Type
Article
Publication Date
1-20-2022
Abstract
Neonatal microcephaly and adult Guillain-Barre syndrome are severe complications of Zika virus (ZIKV) infection. The robustly induced inflammatory cytokine expressions in ZIKV-infected patients may constitute a hallmark for severe disease. In the present study, the potential role of high mobility group box 1 protein (HMGB1) in ZIKV infection was investigated. HMGB1 protein expression was determined by the enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. HMGB1's role in ZIKV infection was also explored using treatment with dexamethasone, an immunomodulatory drug, and HMGB1-knockdown (shHMGB1) Huh7 cells. Results showed that the Huh7 cells were highly susceptible to ZIKV infection. The infection was found to induce HMGB1 nuclear-to-cytoplasmic translocation, resulting in a > 99% increase in the cytosolic HMGB1 expression at 72-h post-infection (h.p.i). The extracellular HMGB1 level was elevated in a time- and multiplicity of infection (MOI)-dependent manner. Treatment of the ZIKV-infected cells with dexamethasone (150 mu M) reduced HMGB1 extracellular release in a dose-dependent manner, with a maximum reduction of 71 +/- 5.84% (P < 0.01). The treatment also reduced virus titers by over 83 +/- 0.50% (P < 0.01). The antiviral effects, however, were not observed in the dexamethasone-treated shHMGB1 cells. These results suggest that translocation of HMGB1 occurred during ZIKV infection and inhibition of the translocation by dexamethasone coincided with a reduction in ZIKV replication. These findings highlight the potential of targeting the localization of HMGB1 in affecting ZIKV infection.
Keywords
Neonatal microcephaly, Adult Guillain-Barre syndrome, Zika virus (ZIKV) infection
Divisions
fac_med,tidrec
Funders
Ministry of Education Malaysia under the Long Term Research Grant Scheme (LRGS MRUN Phase 1) [Grant No: LRGS MRUN/F1/01/2018],Higher Institution Centre of Excellence (HICoE) Program [Grant No: MO002-2019],Fundamental Research Grant Scheme [Grant No: FRGS FP015-2019A]
Publication Title
Scientific Reports
Volume
12
Issue
1
Publisher
Nature Portfolio
Publisher Location
HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY