HSV-1 US3: A Master Mimic Hijacking Host Kinase Networks for Viral Dominance

Authors

• Imran Hossain, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Christella J. Nelson, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Ojasvi Dutta, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Harikrishnan Mohan, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Mehedi Hasan, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Konstantin G. Kousoulas, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA

Document Type

Article

Publication Date

12-4-2025

Publication Title

Journal of Medical Virology

Abstract

Herpes simplex virus type 1 (HSV-1) encodes the serine/threonine kinase US3, a central regulator of host–virus interactions that promotes viral replication, latency, and reactivation. Despite limited sequence homology to cellular kinases such as Akt or PKA, US3 phosphorylates diverse substrates to manipulate multiple pathways. This review summarizes current knowledge of US3 functions across several major areas, including suppression of innate immune responses through modulation of NF-κB, ERK/MAPK, TBK1/IRF3, RIG-I; promotion of cell survival via phosphorylation of canonical Akt substrates such as TSC2, FOXO1/3, and BAD; and facilitation of nuclear egress through modification of lamin A/C, emerin, and the nuclear egress complex proteins UL31 and UL34. By comparing US3's strategies with those of cellular kinases and other viral effectors, this review highlights convergent mechanisms of host manipulation. A comprehensive understanding of US3's multifunctional activities advances insight into HSV-1 pathogenesis and underscores its potential as a target for novel antiviral therapies.

First Page

1

Last Page

16

DOI

10.1002/jmv.70735

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Hossain, Imran; Nelson, Christella J.; Dutta, Ojasvi; Mohan, Harikrishnan; Hasan, Mehedi; and Kousoulas, Konstantin G., "HSV-1 US3: A Master Mimic Hijacking Host Kinase Networks for Viral Dominance" (2025). LSU-LCMC Cancer Center Faculty Publications. 239.
https://digitalscholar.lsuhsc.edu/llcc_facpubs/239
10.1002/jmv.70735