HSV‐1 US3: A Master Mimic Hijacking Host Kinase Networks for Viral Dominance
Year: 2025
Type: article
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.
Source: Journal of Medical Virology
DOI: 10.1002/jmv.70735
Institution: Louisiana State University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,730
OpenAlex ID: W4416985170