Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells

Chin, Kim-Ling and Zainal, Nurhafiza and Sam, Sing-Sin and Hassandarvish, Pouya and Lani, Rafidah and AbuBakar, Sazaly (2022) Intracellular translocation of HMGB1 is important for Zika virus replication in Huh7 cells. Scientific Reports, 12 (1). ISSN 2045-2322, DOI

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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.

Item Type: Article
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]
Uncontrolled Keywords: Neonatal microcephaly; Adult Guillain-Barre syndrome; Zika virus (ZIKV) infection
Subjects: Q Science > Q Science (General)
T Technology > T Technology (General)
Divisions: Faculty of Medicine
Deputy Vice Chancellor (Research & Innovation) Office > Tropical Infectious Diseases Research and Education Centre
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 01 Aug 2022 04:52
Last Modified: 01 Aug 2022 04:52

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