TY - JOUR
T1 - Heat shock protein 70 (Hsp70) mediates Zika virus entry, replication, and egress from host cells
AU - Pujhari, Sujit
AU - Brustolin, Marco
AU - Macias, Vanessa M.
AU - Nissly, Ruth H.
AU - Nomura, Masashi
AU - Kuchipudi, Suresh V.
AU - Rasgon, Jason L.
N1 - Publisher Copyright:
© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Zika virus (ZIKV) is a historically neglected mosquito-borne flavivirus that has caused recent epidemics in the western hemisphere. ZIKV has been associated with severe symptoms including infant microcephaly and Guillain-Barré syndrome, stimulating interest in understanding factors governing ZIKV infection. Heat shock protein 70 (Hsp70) has been shown to be an infection factor for multiple viruses, leading us to investigate the role of Hsp70 in the ZIKV infection process. ZIKV infection induced Hsp70 expression in host cells 48-h post-infection. Inducing Hsp70 expression in mammalian cells increased ZIKV production, whereas inhibiting Hsp70 activity reduced ZIKV viral RNA production and virion release from the cell. Hsp70 was localized both on the cell surface where it could interact with ZIKV during the initial stages of the infection process, and intracellularly where it localized with viral RNA. Blocking cell surface-localized Hsp70 using antibodies decreased ZIKV cell infection rates and production of infectious virus particles, as did competition with recombinant Hsp70 protein. Overall, Hsp70 was found to play a functional role in both the pre- and post-ZIKV infection processes affecting viral entry, replication, and egress. Understanding the interactions between Hsp70 and ZIKV may lead to novel therapeutics for ZIKV infection.
AB - Zika virus (ZIKV) is a historically neglected mosquito-borne flavivirus that has caused recent epidemics in the western hemisphere. ZIKV has been associated with severe symptoms including infant microcephaly and Guillain-Barré syndrome, stimulating interest in understanding factors governing ZIKV infection. Heat shock protein 70 (Hsp70) has been shown to be an infection factor for multiple viruses, leading us to investigate the role of Hsp70 in the ZIKV infection process. ZIKV infection induced Hsp70 expression in host cells 48-h post-infection. Inducing Hsp70 expression in mammalian cells increased ZIKV production, whereas inhibiting Hsp70 activity reduced ZIKV viral RNA production and virion release from the cell. Hsp70 was localized both on the cell surface where it could interact with ZIKV during the initial stages of the infection process, and intracellularly where it localized with viral RNA. Blocking cell surface-localized Hsp70 using antibodies decreased ZIKV cell infection rates and production of infectious virus particles, as did competition with recombinant Hsp70 protein. Overall, Hsp70 was found to play a functional role in both the pre- and post-ZIKV infection processes affecting viral entry, replication, and egress. Understanding the interactions between Hsp70 and ZIKV may lead to novel therapeutics for ZIKV infection.
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U2 - 10.1080/22221751.2018.1557988
DO - 10.1080/22221751.2018.1557988
M3 - Article
C2 - 30866755
AN - SCOPUS:85062835207
SN - 2222-1751
VL - 8
SP - 8
EP - 16
JO - Emerging Microbes and Infections
JF - Emerging Microbes and Infections
IS - 1
ER -
