A functional interaction between GRP78 and Zika virus E protein

Sarawut Khongwichit; Wannapa Sornjai; Kunlakanya Jitobaom; Mingkwan Greenwood; Michael P. Greenwood; Atitaya Hitakarun; Nitwara Wikan; David Murphy; Duncan R. Smith

doi:10.1038/s41598-020-79803-z

journal article Open Access Jan 11, 2021

A functional interaction between GRP78 and Zika virus E protein

Sarawut Khongwichit Wannapa Sornjai Kunlakanya Jitobaom Mingkwan Greenwood Michael P. Greenwood Atitaya Hitakarun

Nitwara Wikan

David Murphy

Duncan R. Smith

Scientific Reports Vol. 11 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/s41598-020-79803-z

Abstract

AbstractZika 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.

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Details

Published: Jan 11, 2021
Vol/Issue: 11(1)
License: View

Authors

Funding

Leverhulme Trust Award: RPG-2017-287

Mahidol University Award: A13/2560

Thailand Graduate Institute of Science and Technology

Royal Golden Jubilee PhD Scholarship

RCUK | Medical Research Council Award: MR/N022807/1

Cite This Article

Sarawut Khongwichit, Wannapa Sornjai, Kunlakanya Jitobaom, et al. (2021). A functional interaction between GRP78 and Zika virus E protein. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-020-79803-z

A functional interaction between GRP78 and Zika virus E protein

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