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Updated: Jun 9, 2025
07:02
Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus KSHV
Published on: September 14, 2010
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Modulators of the Hop-HSP90 Protein-Protein Interaction Disrupt KSHV Lytic Replication
Michael O Okpara1, Michaelone C Vaaltyn1, Jessica L Watson1
1Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry and Microbiology, Rhodes University, Makhanda 6139, South Africa.
ACS Infectious Diseases
|October 30, 2024
Summary
Disrupting the Hop-HSP90 protein interaction inhibits Kaposi sarcoma-associated herpesvirus (KSHV) replication. This study identifies a novel therapeutic target for KSHV by blocking essential chaperone machinery.
Area of Science:
- Virology
- Molecular Biology
- Cellular Biology
Background:
- Viruses often exploit host cell machinery, including chaperones, for replication.
- Heat shock protein 90 (HSP90) and its cochaperone Hop are crucial for Kaposi sarcoma-associated herpesvirus (KSHV) lytic replication.
Purpose of the Study:
- To investigate the disruption of the Hop-HSP90 protein-protein interaction (PPI) as a potential therapeutic strategy against KSHV.
- To explore structure-activity relationships of peptides targeting the Hop-HSP90 PPI.
Main Methods:
- Development and testing of non-natural peptides designed to disrupt the Hop-HSP90 PPI.
- Assessing peptide engagement with the Hop TPR2A domain in cell lysates.
- Evaluating the efficacy of cell-penetrating peptide-tethered inhibitors on KSHV lytic replication in cell culture.
Main Results:
- Peptides selectively targeted the Hop TPR2A domain.
- Cell-penetrating peptide conjugates acted as noncytotoxic inhibitors of KSHV replication.
- Inhibitors reduced viral load, virion production, and KSHV lytic gene expression.
Conclusions:
- The Hop-HSP90 PPI is a promising target for KSHV drug discovery.
- This work advances understanding of viral exploitation of host proteostasis networks.
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