HSP70 Copurifies with Zika Virus Particles

Ronik Khachatoorian; Whitaker Cohn; Anthony Buzzanco; Rana Riahi; Vaithilingaraja Arumugaswami; Asim Dasgupta; Julian P Whitelegge; Samuel W French

doi:10.1016/j.virol.2018.07.009

HSP70 Copurifies with Zika Virus Particles

Virology. 2018 Sep:522:228-233. doi: 10.1016/j.virol.2018.07.009. Epub 2018 Jul 25.

Authors

Ronik Khachatoorian¹, Whitaker Cohn², Anthony Buzzanco³, Rana Riahi⁴, Vaithilingaraja Arumugaswami⁵, Asim Dasgupta⁶, Julian P Whitelegge⁷, Samuel W French⁸

Affiliations

¹ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA, United States. Electronic address: RnKhch@ucla.edu.
² Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States. Electronic address: WhitCohn@yahoo.com.
³ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA, United States. Electronic address: ABuzzanco@gmail.com.
⁴ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA, United States. Electronic address: RanaRiahi@mednet.ucla.edu.
⁵ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, CA, United States. Electronic address: VArumugaswami@mednet.ucla.edu.
⁶ Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, CA, United States; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles, CA, United States; UCLA AIDS Institute, David Geffen School of Medicine at University of California, Los Angeles, CA, United States. Electronic address: Dasgupta@ucla.edu.
⁷ Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States. Electronic address: JPW@chem.ucla.edu.
⁸ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA, United States; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles, CA, United States; UCLA AIDS Institute, David Geffen School of Medicine at University of California, Los Angeles, CA, United States. Electronic address: SFrench@mednet.ucla.edu.

PMID: 30053656
DOI: 10.1016/j.virol.2018.07.009

Abstract

Zika virus (ZIKV) has been identified as a cause of neurologic diseases in infants and Guillain-Barré Syndrome, and currently, no therapeutics or vaccines are approved. In this study, we sought to identify potential host proteins interacting with ZIKV particles to gain better insights into viral infectivity. Viral particles were purified through density-gradient centrifugation and subsequently, size-exclusion chromatography (SEC). Mass spectrometric analyses revealed viral envelope protein and HSP70 to comigrate in only one SEC fraction. Neither of these proteins were found in any other SEC fractions. We then performed neutralization assays and found that incubating viral particles with antibody against HSP70 indeed significantly reduced viral infectivity, while HSC70 antibody did not. Preincubating cells with recombinant HSP70 also decreased viral infectivity. Knockdown and inhibition of HSP70 also significantly diminished viral production. These results implicate HSP70 in the pathogenesis of ZIKV and identify HSP70 as a potential host therapeutic target against ZIKV infection.

Keywords: Heat shock proteins HSP70 HSC70 Zika virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Centrifugation, Density Gradient
Chromatography, Gel
HSP70 Heat-Shock Proteins / isolation & purification*
Host-Pathogen Interactions*
Humans
Mass Spectrometry
Virion / isolation & purification*
Zika Virus / isolation & purification*

Substances

HSP70 Heat-Shock Proteins