A functional interaction between GRP78 and Zika virus E protein

Abstract Zika virus (ZIKV) is a mosquito-transmitted virus that has caused significant public health concerns around the world, partly because of an association with microcephaly in babies born to mothers who were infected with ZIKV during pregnancy. As a recently emerging virus, little is known as...

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Autores principales:	Sarawut Khongwichit, Wannapa Sornjai, Kunlakanya Jitobaom, Mingkwan Greenwood, Michael P. Greenwood, Atitaya Hitakarun, Nitwara Wikan, David Murphy, Duncan R. Smith
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4e35e85d843745a6aaa67e93bac3f2e8
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spelling	oai:doaj.org-article:4e35e85d843745a6aaa67e93bac3f2e82021-12-02T14:12:46ZA functional interaction between GRP78 and Zika virus E protein10.1038/s41598-020-79803-z2045-2322https://doaj.org/article/4e35e85d843745a6aaa67e93bac3f2e82021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79803-zhttps://doaj.org/toc/2045-2322Abstract Zika virus (ZIKV) is a mosquito-transmitted virus that has caused significant public health concerns around the world, partly because of an association with microcephaly in babies born to mothers who were infected with ZIKV during pregnancy. As a recently emerging virus, little is known as to how the virus interacts with the host cell machinery. A yeast-2-hybrid screen for proteins capable of interacting with the ZIKV E protein domain III, the domain responsible for receptor binding, identified 21 proteins, one of which was the predominantly ER resident chaperone protein GRP78. The interaction of GRP78 and ZIKV E was confirmed by co-immunoprecipitation and reciprocal co-immunoprecipitation, and indirect immunofluorescence staining showed intracellular and extracellular co-localization between GRP78 and ZIKV E. Antibodies directed against the N-terminus of GRP78 were able to inhibit ZIKV entry to host cells, resulting in significant reductions in the levels of ZIKV infection and viral production. Consistently, these reductions were also observed after down-regulation of GRP78 by siRNA. These results indicate that GRP78 can play a role mediating ZIKV binding, internalization and replication in cells. GRP78 is a main regulator of the unfolded protein response (UPR), and the study showed that expression of GRP78 was up-regulated, and the UPR was activated. Increases in CHOP expression, and activation of caspases 7 and 9 were also shown in response to ZIKV infection. Overall these results indicate that the interaction between GRP78 and ZIKV E protein plays an important role in ZIKV infection and replication, and may be a potential therapeutic target.Sarawut KhongwichitWannapa SornjaiKunlakanya JitobaomMingkwan GreenwoodMichael P. GreenwoodAtitaya HitakarunNitwara WikanDavid MurphyDuncan R. SmithNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarawut Khongwichit Wannapa Sornjai Kunlakanya Jitobaom Mingkwan Greenwood Michael P. Greenwood Atitaya Hitakarun Nitwara Wikan David Murphy Duncan R. Smith A functional interaction between GRP78 and Zika virus E protein
description	Abstract Zika virus (ZIKV) is a mosquito-transmitted virus that has caused significant public health concerns around the world, partly because of an association with microcephaly in babies born to mothers who were infected with ZIKV during pregnancy. As a recently emerging virus, little is known as to how the virus interacts with the host cell machinery. A yeast-2-hybrid screen for proteins capable of interacting with the ZIKV E protein domain III, the domain responsible for receptor binding, identified 21 proteins, one of which was the predominantly ER resident chaperone protein GRP78. The interaction of GRP78 and ZIKV E was confirmed by co-immunoprecipitation and reciprocal co-immunoprecipitation, and indirect immunofluorescence staining showed intracellular and extracellular co-localization between GRP78 and ZIKV E. Antibodies directed against the N-terminus of GRP78 were able to inhibit ZIKV entry to host cells, resulting in significant reductions in the levels of ZIKV infection and viral production. Consistently, these reductions were also observed after down-regulation of GRP78 by siRNA. These results indicate that GRP78 can play a role mediating ZIKV binding, internalization and replication in cells. GRP78 is a main regulator of the unfolded protein response (UPR), and the study showed that expression of GRP78 was up-regulated, and the UPR was activated. Increases in CHOP expression, and activation of caspases 7 and 9 were also shown in response to ZIKV infection. Overall these results indicate that the interaction between GRP78 and ZIKV E protein plays an important role in ZIKV infection and replication, and may be a potential therapeutic target.
format	article
author	Sarawut Khongwichit Wannapa Sornjai Kunlakanya Jitobaom Mingkwan Greenwood Michael P. Greenwood Atitaya Hitakarun Nitwara Wikan David Murphy Duncan R. Smith
author_facet	Sarawut Khongwichit Wannapa Sornjai Kunlakanya Jitobaom Mingkwan Greenwood Michael P. Greenwood Atitaya Hitakarun Nitwara Wikan David Murphy Duncan R. Smith
author_sort	Sarawut Khongwichit
title	A functional interaction between GRP78 and Zika virus E protein
title_short	A functional interaction between GRP78 and Zika virus E protein
title_full	A functional interaction between GRP78 and Zika virus E protein
title_fullStr	A functional interaction between GRP78 and Zika virus E protein
title_full_unstemmed	A functional interaction between GRP78 and Zika virus E protein
title_sort	functional interaction between grp78 and zika virus e protein
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4e35e85d843745a6aaa67e93bac3f2e8
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A functional interaction between GRP78 and Zika virus E protein

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