Heat shock protein 70 (Hsp70) mediates Zika virus entry, replication, and egress from host cells

Sujit Pujhari, Marco Brustolin, Vanessa M Macias, Ruth H Nissly, Masashi Nomura, Suresh V Kuchipudi, Jason L Rasgon

Research output: Contribution to journalA1: Web of Science-articlepeer-review

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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.

Original languageEnglish
JournalEmerging Microbes & Infections
Issue number1
Pages (from-to)8-16
Number of pages9
Publication statusPublished - 2019
Externally publishedYes


  • Animals
  • Antibodies/pharmacology
  • Cell Line
  • Chlorocebus aethiops
  • Gene Expression Regulation/drug effects
  • HEK293 Cells
  • HSP70 Heat-Shock Proteins/antagonists & inhibitors
  • Humans
  • Pyridines/pharmacology
  • Thiazoles/pharmacology
  • Vero Cells
  • Virus Internalization/drug effects
  • Virus Release/drug effects
  • Virus Replication/drug effects
  • Zika Virus/drug effects
  • Zika Virus Infection/metabolism


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