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

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Zika virus (ZIKV), a mosquito-borne flavivirus, has caused significant epidemics.
• ZIKV infection is linked to severe neurological conditions like microcephaly and Guillain-Barré syndrome.
• Heat shock protein 70 (Hsp70) is implicated as a factor in the infection mechanisms of various viruses.

Purpose of the Study:

• To investigate the role of Heat shock protein 70 (Hsp70) in the Zika virus (ZIKV) infection cycle.
• To determine how Hsp70 influences ZIKV entry, replication, and release from host cells.

Main Methods:

• Monitoring Hsp70 expression levels in host cells post-ZIKV infection.
• Manipulating Hsp70 expression and activity to assess its impact on viral production.
• Utilizing immunofluorescence and antibody-blocking assays to determine Hsp70 localization and its role in viral interaction.
• Employing recombinant Hsp70 protein for competitive inhibition studies.

Main Results:

• ZIKV infection upregulated Hsp70 expression in host cells.
• Enhanced Hsp70 expression increased ZIKV production, while inhibition reduced viral RNA and virion release.
• Hsp70 was found on the cell surface, interacting with ZIKV, and intracellularly with viral RNA.
• Blocking cell surface Hsp70 or competing with recombinant Hsp70 decreased ZIKV infection rates and viral particle production.

Conclusions:

• Hsp70 plays a critical role in multiple stages of the ZIKV life cycle, including entry, replication, and egress.
• Targeting Hsp70 interactions with ZIKV presents a potential strategy for developing novel antiviral therapies against Zika virus.