Basic Life Science Research Associate, Biology
Zika Virus Dependence on Host Hsp70 Provides a Protective Strategy against Infection and Disease.
2019; 26 (4): 906
The spread of mosquito-borne Zika virus (ZIKV), which causes neurological disorders and microcephaly, highlights the need for countermeasures against sudden viral epidemics. Here, we tested the concept that drugs targeting host proteostasis provide effective antivirals. We show that different cytosolic Hsp70 isoforms are recruited to ZIKV-induced compartments and are required for virus replication at pre- and post-entry steps. Drugs targeting Hsp70 significantly reduce replication of different ZIKV strains in human and mosquito cells, including human neural stem cells and a placental trophoblast cell line, at doses without appreciable toxicity to the host cell. By targeting several ZIKV functions, including entry, establishment of active replication complexes, and capsid assembly, Hsp70 inhibitors are refractory to the emergence of drug-resistant virus. Importantly, these drugs protected mouse models from ZIKV infection, reducing viremia, mortality, and disease symptoms. Hsp70 inhibitors are thus attractive candidates for ZIKV therapeutics with the added benefit of a broad spectrum of action.
View details for DOI 10.1016/j.celrep.2018.12.095
View details for PubMedID 30673613
- Defining Hsp70 Subnetworks in Dengue Virus Replication Reveals Key Vulnerability in Flavivirus Infection. Cell 2015; 163 (5): 1108-1123
The significance of Hsp70 subnetwork for Dengue virus lifecycle.
2015; 65 (2): 179-186
Viruses hijack host machineries for replicating themselves efficiently. Host protein quality control machineries (QC) not only assist protein folding to form bona fide proteins with active functions but also get rid of un/misfolded proteins via degradation to maintain the protein homeostasis. Previous studies have reported that viruses utilize QC at various steps for their lifecycles. Recently we defined Hsp70s and their cochaperones, DnaJs functions on Dengue lifecycle. Here we summarize the significance of QC on Dengue virus.
View details for PubMedID 27760916
Broad action of Hsp90 as a host chaperone required for viral replication
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
2012; 1823 (3): 698-706
Viruses are intracellular pathogens responsible for a vast number of human diseases. Due to their small genome size, viruses rely primarily on the biosynthetic apparatus of the host for their replication. Recent work has shown that the molecular chaperone Hsp90 is nearly universally required for viral protein homeostasis. As observed for many endogenous cellular proteins, numerous different viral proteins have been shown to require Hsp90 for their folding, assembly, and maturation. Importantly, the unique characteristics of viral replication cause viruses to be hypersensitive to Hsp90 inhibition, thus providing a novel therapeutic avenue for the development of broad-spectrum antiviral drugs. The major developments in this emerging field are hereby discussed. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).
View details for DOI 10.1016/j.bbamcr.2011.11.007
View details for Web of Science ID 000301628700012
View details for PubMedID 22154817