Host cell entry receptors for HSV and cellular replication machinery

This target profile represents the collective host and viral components essential for the infection cycle of Herpes Simplex Virus (HSV). Host cell entry is initiated by the binding of viral glycoproteins to specific cell surface receptors, primarily Nectin-1 (CD111), Herpesvirus Entry Mediator (HVEM), and 3-O-sulfated heparan sulfate, which facilitate membrane fusion and capsid release into the cytoplasm (Agelidis & Shukla, 2015). Once the viral genome enters the nucleus, it utilizes a specialized replication machinery consisting of the viral DNA polymerase (UL30) and its processivity factor (UL42), as well as the heterotrimeric helicase-primase complex (UL5/UL8/UL52) (Weller & Coen, 2012). The virus also hijacks host cellular replication machinery, such as Proliferating Cell Nuclear Antigen (PCNA), to support efficient DNA synthesis and chromatin remodeling (Harland et al., 2003). Therapeutic agents targeting these processes include nucleoside analogs like acyclovir, which inhibit the viral DNA polymerase, and newer non-nucleoside inhibitors like pritelivir that target the helicase-primase complex to overcome resistance and improve clinical outcomes in HSV-1 and HSV-2 infections (Wald et al., 2014).

Other names

HSV entry and replication factorsNectin-1 (CD111)Herpesvirus entry mediator (HVEM)3-O-sulfated heparan sulfateViral DNA polymerase complex (UL30/UL42)Helicase-primase complex (UL5/UL8/UL52)Proliferating cell nuclear antigen (PCNA)

Inhibition of viral DNA polymerase through nucleoside/nucleotide analogs or pyrophosphate competition, inhibition of the viral helicase-primase complex, and prevention of viral-host membrane fusion or receptor binding.