Staff View: Cell surface α2,3-linked sialic acid facilitates Zika virus internalization

Cell surface α2,3-linked sialic acid facilitates Zika virus internalization

The emergence of neurotropic Zika virus (ZIKV) raised a public health emergency of global concern. ZIKV can cross the placental barrier and infect foetal brains, resulting in microcephaly, but the pathogenesis of ZIKV is poorly understood. With recent findings reporting AXL as a type I interferon an...

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Main Authors:	Tan, Chee Wah, Huan Hor, Catherine Hong, Kwek, Swee Sen, Tee, Han Kang, Sam, I-Ching, Goh, Eyleen L.K., Ooi, Eng Eong, Chan, Yoke Fun, Wang, Lin Fa
Format:	Article
Published:	Taylor & Francis Open 2019
Subjects:	R Medicine
Online Access:	http://eprints.um.edu.my/23314/ https://doi.org/10.1080/22221751.2019.1590130
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spelling	my.um.eprints.233142020-01-06T02:40:26Z http://eprints.um.edu.my/23314/ Cell surface α2,3-linked sialic acid facilitates Zika virus internalization Tan, Chee Wah Huan Hor, Catherine Hong Kwek, Swee Sen Tee, Han Kang Sam, I-Ching Goh, Eyleen L.K. Ooi, Eng Eong Chan, Yoke Fun Wang, Lin Fa R Medicine The emergence of neurotropic Zika virus (ZIKV) raised a public health emergency of global concern. ZIKV can cross the placental barrier and infect foetal brains, resulting in microcephaly, but the pathogenesis of ZIKV is poorly understood. With recent findings reporting AXL as a type I interferon antagonist rather than an entry receptor, the exact entry mechanism remains unresolved. Here we report that cell surface sialic acid plays an important role in ZIKV infection. Removal of cell surface sialic acid by neuraminidase significantly abolished ZIKV infection in Vero cells and human induced-pluripotent stem cells-derived neural progenitor cells. Furthermore, knockout of the sialic acid biosynthesis gene encoding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase resulted in significantly less ZIKV infection of both African and Asian lineages. Huh7 cells deficient in α2,3-linked sialic acid through knockout of ST3 β-galactoside-α2,3-sialyltransferase 4 had significantly reduced ZIKV infection. Removal of membrane-bound, un-internalized virus with pronase treatment revealed the role of sialic acid in ZIKV internalization but not attachment. Sialyllactose inhibition studies showed that there is no direct interaction between sialic acid and ZIKV, implying that sialic acid could be mediating ZIKV-receptor complex internalization. Identification of α2,3-linked sialic acid as an important host factor for ZIKV internalization provides new insight into ZIKV infection and pathogenesis. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. Taylor & Francis Open 2019 Article PeerReviewed Tan, Chee Wah and Huan Hor, Catherine Hong and Kwek, Swee Sen and Tee, Han Kang and Sam, I-Ching and Goh, Eyleen L.K. and Ooi, Eng Eong and Chan, Yoke Fun and Wang, Lin Fa (2019) Cell surface α2,3-linked sialic acid facilitates Zika virus internalization. Emerging Microbes & Infections, 8 (1). pp. 426-437. ISSN 2222-1751 https://doi.org/10.1080/22221751.2019.1590130 doi:10.1080/22221751.2019.1590130
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	R Medicine
spellingShingle	R Medicine Tan, Chee Wah Huan Hor, Catherine Hong Kwek, Swee Sen Tee, Han Kang Sam, I-Ching Goh, Eyleen L.K. Ooi, Eng Eong Chan, Yoke Fun Wang, Lin Fa Cell surface α2,3-linked sialic acid facilitates Zika virus internalization
description	The emergence of neurotropic Zika virus (ZIKV) raised a public health emergency of global concern. ZIKV can cross the placental barrier and infect foetal brains, resulting in microcephaly, but the pathogenesis of ZIKV is poorly understood. With recent findings reporting AXL as a type I interferon antagonist rather than an entry receptor, the exact entry mechanism remains unresolved. Here we report that cell surface sialic acid plays an important role in ZIKV infection. Removal of cell surface sialic acid by neuraminidase significantly abolished ZIKV infection in Vero cells and human induced-pluripotent stem cells-derived neural progenitor cells. Furthermore, knockout of the sialic acid biosynthesis gene encoding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase resulted in significantly less ZIKV infection of both African and Asian lineages. Huh7 cells deficient in α2,3-linked sialic acid through knockout of ST3 β-galactoside-α2,3-sialyltransferase 4 had significantly reduced ZIKV infection. Removal of membrane-bound, un-internalized virus with pronase treatment revealed the role of sialic acid in ZIKV internalization but not attachment. Sialyllactose inhibition studies showed that there is no direct interaction between sialic acid and ZIKV, implying that sialic acid could be mediating ZIKV-receptor complex internalization. Identification of α2,3-linked sialic acid as an important host factor for ZIKV internalization provides new insight into ZIKV infection and pathogenesis. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.
format	Article
author	Tan, Chee Wah Huan Hor, Catherine Hong Kwek, Swee Sen Tee, Han Kang Sam, I-Ching Goh, Eyleen L.K. Ooi, Eng Eong Chan, Yoke Fun Wang, Lin Fa
author_facet	Tan, Chee Wah Huan Hor, Catherine Hong Kwek, Swee Sen Tee, Han Kang Sam, I-Ching Goh, Eyleen L.K. Ooi, Eng Eong Chan, Yoke Fun Wang, Lin Fa
author_sort	Tan, Chee Wah
title	Cell surface α2,3-linked sialic acid facilitates Zika virus internalization
title_short	Cell surface α2,3-linked sialic acid facilitates Zika virus internalization
title_full	Cell surface α2,3-linked sialic acid facilitates Zika virus internalization
title_fullStr	Cell surface α2,3-linked sialic acid facilitates Zika virus internalization
title_full_unstemmed	Cell surface α2,3-linked sialic acid facilitates Zika virus internalization
title_sort	cell surface α2,3-linked sialic acid facilitates zika virus internalization
publisher	Taylor & Francis Open
publishDate	2019
url	http://eprints.um.edu.my/23314/ https://doi.org/10.1080/22221751.2019.1590130
_version_	1654960716051906560
score	13.211869

Cell surface α2,3-linked sialic acid facilitates Zika virus internalization

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