HSV-1

Herpes simplex virus type 1 (HSV-1) is a neurotropic DNA virus that exploits host cellular machinery to ensure efficient replication^[1][2]. Mechanistically, HSV-1 hijacks the cyclin-dependent kinase (CDK)-4EBP1 signaling axis to disrupt host translational control, promoting viral protein synthesis^[2]. The virus also induces filopodia formation in activated T lymphocytes through actin polymerization mediated by Cdc42, enhancing viral entry and dissemination^[3]. HSV-1 modulates host innate immunity by targeting the STING pathway, including alternative splice isoforms such as STING-∆N, which suppress interferon induction and autophagy, facilitating viral replication^[4]. Heat-shock protein 90α (Hsp90α) is critical for maintaining VP16 stability, enabling transactivation of immediate-early α genes, and thereby supporting lytic infection^[5]. Stress conditions and corticosterone increase HSV-1 susceptibility via autophagic degradation of PML, further highlighting host pathway exploitation^[1]. In addition, HSV-1 replication engages JNK/p38 MAP kinase pathways and BRD4 redistribution, demonstrating reliance on stress-activated signaling for viral transcriptional elongation^[6][7]. Distinct from related isoforms, truncated STING variants lack transmembrane domains and selectively inhibit wild-type STING signaling^[8][4]. Pharmacologically, small-molecule inhibitors like BX-795 or CDK inhibitors such as GW8510 suppress HSV-1 replication by interfering with these host-dependent pathways, providing experimental tools for mechanistic studies^[6][2].