Host Ubiquitin-Specific Proteases Regulate All Stages of Herpesvirus Infection
- 1Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA
Abstract
Herpesviruses are a large group of double-stranded-DNA viruses that replicate their genomes in the nucleus, forming large replication compartments during lytic infection. Herpesviruses are known to modulate host DNA replication and DNA damage-repair proteins to promote their replication. Ubiquitination is a cellular process that can alter protein stability, localization, and availability, including that of multiple proteins involved in genome maintenance. Ubiquitin-specific proteases (USPs) are a class of deubiquitinating enzymes (DUBs) that counter this process by removing ubiquitin chains, thus acting as another level of regulation. Proteins from each of the three herpesvirus subfamilies (alpha-, beta-, and gammaherpesviruses) have been reported to interact with at least one host USP, and USP7 in particular is reported as a target in representatives of all three subfamilies. In this review, we give an up-to-date summary of herpesviruses–USPs interactions, with special emphasis on DNA replication, and how these interactions could shape infection outcomes. We also examine published proteomic datasets for herpesvirus-driven host-proteome modulation and offer a framework for future directions to prioritize potentially important, understudied USPs. Lastly, we visit herpesvirus-encoded DUBs and highlight their roles in viral replication by remodeling ubiquitin signaling, discussing viral DUBs and virus–USP interfaces as proposed antiviral targets.
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BibTeX
@article{maarouf2026host,
title = {{Host Ubiquitin-Specific Proteases Regulate All Stages of Herpesvirus Infection}},
author = {Mohamed Maarouf and Christopher S. Peterson and Kareem N. Mohni},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219631},
url = {https://www.mdpi.com/1422-0067/27/21/9631},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Host Ubiquitin-Specific Proteases Regulate All Stages of Herpesvirus Infection
AU - Mohamed Maarouf
AU - Christopher S. Peterson
AU - Kareem N. Mohni
PY - 2026
DA - 2026/10/28
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219631
UR - https://www.mdpi.com/1422-0067/27/21/9631
AB - Herpesviruses are a large group of double-stranded-DNA viruses that replicate their genomes in the nucleus, forming large replication compartments during lytic infection. Herpesviruses are known to modulate host DNA replication and DNA damage-repair proteins to promote their replication. Ubiquitination is a cellular process that can alter protein stability, localization, and availability, including that of multiple proteins involved in genome maintenance. Ubiquitin-specific proteases (USPs) are a class of deubiquitinating enzymes (DUBs) that counter this process by removing ubiquitin chains, thus acting as another level of regulation. Proteins from each of the three herpesvirus subfamilies (alpha-, beta-, and gammaherpesviruses) have been reported to interact with at least one host USP, and USP7 in particular is reported as a target in representatives of all three subfamilies. In this review, we give an up-to-date summary of herpesviruses–USPs interactions, with special emphasis on DNA replication, and how these interactions could shape infection outcomes. We also examine published proteomic datasets for herpesvirus-driven host-proteome modulation and offer a framework for future directions to prioritize potentially important, understudied USPs. Lastly, we visit herpesvirus-encoded DUBs and highlight their roles in viral replication by remodeling ubiquitin signaling, discussing viral DUBs and virus–USP interfaces as proposed antiviral targets.
SN - 1422-0067
ER -