# Defining the role of Host Hsp70 Subnetworks in Dengue Virus Replication

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $496,530

## Abstract

Defining the role of Host Hsp70 Subnetworks in Dengue Virus Replication
Abstract: Viral protein folding and homeostasis depends entirely on the machinery of the host cell. Here we
define the dependence of Dengue virus (DENV) on the complex network of Hsp70 chaperones and
cochaperones which mediate distinct steps of the virus life cycle. We find that several cytosolic Hsp70 isoforms
are required at multiple steps of the viral life cycle to prevent viral protein degradation, promote virion assembly
and support viral enzyme function. At each step, Hsp70 function is specified by distinct subnetworks of
cofactors, called DnaJs and NEFs, that modulate Hsp70 action and localization at each step. We
hypothesize that combinations of DnaJs and NEFs dictate the specific cellular locations, substrate
specificities and downstream effectors of Hsp70 in viral replication. We propose to define the mechanism
and function of Hsp70 subnetworks in DENV replication through the integration of genetic and proteomic
analyses with biochemical and cell biological experiments. Specifically we propose to: (1) Define the
mechanism and function of DnaJs in DENV replication; (2) Dissect the role and mechanism of Hsp70
NEFs in DENV replication and (3) Define the mechanism of restriction by the Bag6-centered network.
Defining the chaperone subnetworks required for distinct steps of DENV replication will provide new insights
into key aspects of the cell biology and molecular mechanism of viral infection. Importantly, Hsp70 provides a
susceptible node for antiviral drugs, since compounds inhibiting the Hsp70 cycle blocks DENV infection with
negligible toxicity to the host. Our work will thus identify novel targets for pharmacological antiviral intervention
and uncover unanticipated cellular mechanisms for viral restriction.

## Key facts

- **NIH application ID:** 10054971
- **Project number:** 5R01AI127447-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Judith Frydman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $496,530
- **Award type:** 5
- **Project period:** 2016-11-14 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054971

## Citation

> US National Institutes of Health, RePORTER application 10054971, Defining the role of Host Hsp70 Subnetworks in Dengue Virus Replication (5R01AI127447-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10054971. Licensed CC0.

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