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Characterization of Zika virus endocytic pathways in human glioblastoma cells

Li, M; Zhang, D; Li, C; Zheng, Z; Fu, M; Ni, F; Liu, Y; Du, T; Wang, H; Griffin, GE; et al. Li, M; Zhang, D; Li, C; Zheng, Z; Fu, M; Ni, F; Liu, Y; Du, T; Wang, H; Griffin, GE; Zhang, M; Hu, Q (2020) Characterization of Zika virus endocytic pathways in human glioblastoma cells. Frontiers in Microbiology, 11. p. 242. ISSN 1664-302X https://doi.org/10.3389/fmicb.2020.00242
SGUL Authors: Hu, Qinxue

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Abstract

Zika virus (ZIKV) infections can cause microcephaly and neurological disorders. However, the early infection events of ZIKV in neural cells remain to be characterized. Here, by using a combination of pharmacological and molecular approaches and the human glioblastoma cell T98G as a model, we first observed that ZIKV infection was inhibited by chloroquine and NH4Cl, indicating a requirement of low intracellular pH. We further showed that dynamin is required as the ZIKV entry was affected by the specific inhibitor dynasore, small interfering RNA (siRNA) knockdown of dynamin, or by expressing the dominant-negative K44A mutant. Moreover, the ZIKV entry was significantly inhibited by chlorpromazine, pitstop2, or siRNA knockdown of clathrin heavy chain, indicating an involvement of clathrin-mediated endocytosis. In addition, genistein treatment, siRNA knockdown of caveolin-1, or overexpression of a dominant-negative caveolin mutant impacted the ZIKV entry, with ZIKV particles being observed to colocalize with caveolin-1, implying that caveola endocytosis can also be involved. Furthermore, we found that the endocytosis of ZIKV is dependent on membrane cholesterol, microtubules, and actin cytoskeleton. Importantly, ZIKV infection was inhibited by silencing of Rab5 and Rab7, while confocal microscopy showed that ZIKV particles localized in Rab5- and Rab7-postive endosomes. These results indicated that, after internalization, ZIKV likely moves to Rab5-positive early endosome and Rab7-positive late endosomes before delivering its RNA into the cytoplasm. Taken together, our study, for the first time, described the early infection events of ZIKV in human glioblastoma cell T98G.

Item Type: Article
Additional Information: Copyright © 2020 Li, Zhang, Li, Zheng, Fu, Ni, Liu, Du, Wang, Griffin, Zhang and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Frontiers in Microbiology
ISSN: 1664-302X
Dates:
DateEvent
6 March 2020Published
31 January 2020Accepted
Projects:
Project IDFunderFunder ID
2018ZX10301406-002National Mega-Projects against Infectious DiseasesUNSPECIFIED
2018ZX10734401-018-003National Mega-Projects against Infectious DiseasesUNSPECIFIED
2018ZX10301405-003National Mega-Projects against Infectious DiseasesUNSPECIFIED
UNSPECIFIEDEmergency Prevention and Control Capacity Program for New Severe Infectious diseases of National Institute for Viral Disease Control and PreventionUNSPECIFIED
UNSPECIFIED135 Strategic Program of Chinese Academy of SciencesUNSPECIFIED
UNSPECIFIEDHotung TrustUNSPECIFIED
URI: http://openaccess.sgul.ac.uk/id/eprint/111715
Publisher's version: https://doi.org/10.3389/fmicb.2020.00242

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