Targeting the Inositol-Requiring Enzyme-1 Pathway Efficiently Reverts Zika Virus-Induced Neurogenesis and Spermatogenesis Marker Perturbations

Chu, Hin; Yuen, Terrence Tsz‐Tai; Chik, Kenn Ka Heng; Yuan, Shuofeng; Shuai, Huiping; Zou, Zijiao; Wang, Yixin; Zhu, Zheng; Yang, Dong; Poon, Vincent Kwok Man; Chan, C. K.; Zhou, Jie; Yin, Feifei; Kok, Kin‐Hang; Yuen, Kwok‐Yung; Chan, Jasper Fuk‐Woo

doi:10.1021/acsinfecdis.9b00526

Cited by 8 publications

(5 citation statements)

References 53 publications

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“…VeroE6 was purchased from the American Type Culture Collection (ATCC) and maintained in Dulcecco’s Modified Eagle’s Medium (DMEM), supplemented with 10% fetal bovine serum (FBS), 100 units/mL of penicillin and 100μg/mL of streptomycin (5%CO 2 at 37°C). ZIKV PR (Puerto Rico strain PRVABC59) was obtained from a patient in the recent South American epidemic (kindly provided by Brandy Russell and Barbara Johnson, Centers for Disease Control and Prevention, USA) and ZIKV U (ZIKVAF-976 Uganda strain) was isolated from a nonhuman primate in Uganda in 1947 (kindly provided by Tatjana Avšič Županc, University of Ljubljana, Slovenia, the European Virus Archive) [ 27 , 28 ]. Yellow fever virus 17D (YFV) was available in our laboratory and cultured as previously described [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

STAT2-dependent restriction of Zika virus by human macrophages but not dendritic cells

Yang

Chu

Lü

et al. 2021

Emerging Microbes & Infections

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STAT2-dependent restriction of Zika virus by human macrophages but not dendritic cells ABSTRACTZika virus (ZIKV) is an emerging mosquito-borne flavivirus that poses significant threats to global public health. Macrophages and dendritic cells are both key sentinel cells in the host immune response and play critical roles in the pathogenesis of flavivirus infections. Recent studies showed that ZIKV could productively infect monocyte-derived dendritic cells (moDCs), but the role of macrophages in ZIKV infection remains incompletely understood. In this study, we first compared ZIKV infection in monocyte-derived macrophages (MDMs) and moDCs derived from the same donors. We demonstrated that while both MDMs and moDCs were susceptible to epidemic (Puerto Rico) and pre-epidemic (Uganda) strains of ZIKV, virus replication was largely restricted in MDMs but not in moDCs. ZIKV induced significant apoptosis in moDCs but not MDMs. The restricted virus replication in MDMs was not due to inefficient virus entry but was related to post-entry events in the viral replication cycle. In stark contrast with moDCs, ZIKV failed to inhibit STAT1 and STAT2 phosphorylation in MDMs. This resulted in the lack of efficient antagonism of the host type I interferon-mediated antiviral responses. Importantly, depletion of STAT2 but not STAT1 in MDMs significantly rescued the replication of ZIKV and the prototype flavivirus yellow fever virus. Overall, our findings revealed a differential interplay between macrophages and dendritic cells with ZIKV. While dendritic cells may be exploited by ZIKV to facilitate virus replication, macrophages restricted ZIKV infection.

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Section: Methodsmentioning

confidence: 99%

STAT2-dependent restriction of Zika virus by human macrophages but not dendritic cells

Yang

Chu

Lü

et al. 2021

Emerging Microbes & Infections

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“…Gene expression was quantified by qPCR with LightCycler 480 SYBR Green I Master (Roche) and normalized to mock-infected controls or GAPDH gene expression as we previously described. [21][22][23] Primer sequences used in this study were listed in supplementary Table 1.…”

Section: Rna Extraction and Quantitative Reverse Transcription Polymementioning

confidence: 99%

Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-β and IFN inducer

Shuai

Chu

Hou

et al. 2020

Journal of Infection

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Objectives: Respiratory and intestinal tract are two primary target organs of SARS-CoV-2 infection. However, detailed characterization of the host-virus interplay in infected human lung and intestinal epithelial cells is lacking. Methods: We utilized immunofluorescence assays, flow cytometry, and RT-qPCR to delineate the virological features and the innate immune response of the host cells against SARS-CoV-2 infection in two prototype human cell lines representing the human lung (Calu3) and intestinal (Caco2) epithelium when compared with SARS-CoV. Results: Lung epithelial cells were significantly more susceptible to SARS-CoV-2 compared to SARS-CoV. However, SARS-CoV-2 infection induced an attenuated pro-inflammatory cytokines/chemokines induction and type I and type II IFN responses. A single dose of 10 U/mL interferon-β (IFN β) pretreatment potently protected both Calu3 and Caco2 against SARS-CoV-2 infection. Interestingly, SARS-CoV-2 was more sensitive to the pretreatment with IFN β and IFN inducer than SARS-CoV in Calu3. Conclusions: Despite robust infection in both human lung and intestinal epithelial cells, SARS-CoV-2 could attenuate the virus-induced pro-inflammatory response and IFN response. Pre-activation of the type I IFN signaling pathway primed a highly efficient antiviral response in the host against SARS-CoV-2 infection, which could serve as a potential therapeutic and prophylactic maneuver to COVID-19 patients.

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“…Cell viability was quantified by CellTiter-Glo luminescent cell viability assay kit (Promega, USA) as we previously described [30]. Caco2 cells were treated with selected inhibitors at a series of concentration (0-100µM) for 24 hours, and followed by manufacturer's instructions to detect luminescent signal using the Victor X3 2030 Multilabel reader (Perkin Elmer, USA).…”

Section: Cell Viability Assay (Cc 50 )mentioning

confidence: 99%

Targeting ACLY efficiently inhibits SARS-CoV-2 replication

Yuen¹,

Chan²,

Yan³

et al. 2022

Int. J. Biol. Sci.

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The Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the biggest public health challenge the world has witnessed in the past decades. SARS-CoV-2 undergoes constant mutations and new variants of concerns (VOCs) with altered transmissibility, virulence, and/or susceptibility to vaccines and therapeutics continue to emerge. Detailed analysis of host factors involved in virus replication may help to identify novel treatment targets. In this study, we dissected the metabolome derived from COVID-19 patients to identify key host factors that are required for efficient SARS-CoV-2 replication. Through a series of metabolomic analyses, in vitro, and in vivo investigations, we identified ATP citrate lyase (ACLY) as a novel host factor required for efficient replication of SARS-CoV-2 wild-type and variants, including Omicron. ACLY should be further explored as a novel intervention target for COVID-19.

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Targeting the Inositol-Requiring Enzyme-1 Pathway Efficiently Reverts Zika Virus-Induced Neurogenesis and Spermatogenesis Marker Perturbations

Cited by 8 publications

References 53 publications

STAT2-dependent restriction of Zika virus by human macrophages but not dendritic cells

STAT2-dependent restriction of Zika virus by human macrophages but not dendritic cells

Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-β and IFN inducer

Targeting ACLY efficiently inhibits SARS-CoV-2 replication

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