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 Varma Kuchipudi, Jason Laurence Rasgon

Research output: Contribution to journalArticle

Abstract

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 (US)
Pages (from-to)8-16
Number of pages9
JournalEmerging Microbes and Infections
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Virus Release
Virus Internalization
HSP70 Heat-Shock Proteins
Virus Replication
Viral RNA
Virion
Infection
Zika Virus
Flavivirus
Microcephaly
Culicidae
Recombinant Proteins
Zika Virus Infection
Viruses

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Epidemiology
  • Microbiology
  • Immunology
  • Drug Discovery
  • Virology
  • Infectious Diseases

Cite this

@article{ec30a48236cc4f4783e0eba7b42ce78e,
title = "Heat shock protein 70 (Hsp70) mediates Zika virus entry, replication, and egress from host cells",
abstract = "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-Barr{\'e} 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.",
author = "Sujit Pujhari and Marco Brustolin and Macias, {Vanessa M.} and Nissly, {Ruth H.} and Masashi Nomura and Kuchipudi, {Suresh Varma} and Rasgon, {Jason Laurence}",
year = "2019",
month = "1",
day = "1",
doi = "10.1080/22221751.2018.1557988",
language = "English (US)",
volume = "8",
pages = "8--16",
journal = "Emerging Microbes and Infections",
issn = "2222-1751",
publisher = "Nature Publishing Group",
number = "1",

}

Heat shock protein 70 (Hsp70) mediates Zika virus entry, replication, and egress from host cells. / Pujhari, Sujit; Brustolin, Marco; Macias, Vanessa M.; Nissly, Ruth H.; Nomura, Masashi; Kuchipudi, Suresh Varma; Rasgon, Jason Laurence.

In: Emerging Microbes and Infections, Vol. 8, No. 1, 01.01.2019, p. 8-16.

Research output: Contribution to journalArticle

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 Varma

AU - Rasgon, Jason Laurence

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.

UR - http://www.scopus.com/inward/record.url?scp=85062835207&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062835207&partnerID=8YFLogxK

U2 - 10.1080/22221751.2018.1557988

DO - 10.1080/22221751.2018.1557988

M3 - Article

C2 - 30866755

AN - SCOPUS:85062835207

VL - 8

SP - 8

EP - 16

JO - Emerging Microbes and Infections

JF - Emerging Microbes and Infections

SN - 2222-1751

IS - 1

ER -