Herpes simplex virus early infection stages

The early infection stages of Herpes Simplex Virus (HSV) encompass the critical steps from initial viral attachment to the host cell to the replication of the viral genome [1]. This process begins with the binding of viral glycoproteins (such as gC and gB) to heparan sulfate proteoglycans on the cell surface, followed by the interaction of glycoprotein D (gD) with specific entry receptors like HVEM (TNFRSF14) or Nectin-1 (PVRL1) [1, 5]. These interactions trigger membrane fusion, mediated by the gB and gH/gL complex, allowing the viral capsid to enter the cytoplasm and transport the DNA to the nucleus [1]. Once in the nucleus, immediate-early and early viral proteins are expressed; early proteins include essential enzymes like DNA polymerase (UL30) and the helicase-primase complex (UL5/UL8/UL52), which are responsible for viral DNA synthesis [1, 4]. Therapeutic intervention at these stages is highly effective: entry inhibitors like docosanol prevent viral fusion by interfering with host cell surface phospholipids [1], while nucleoside analogs like acyclovir and helicase-primase inhibitors like pritelivir disrupt the early protein-mediated replication process [1, 2, 4]. Targeting these early events is the primary strategy for managing acute outbreaks and reducing viral shedding, although these treatments do not eliminate the latent viral reservoir in sensory ganglia [3, 5].

Other names

HSV early infectionHSV entry and early replicationHerpes simplex virus entryHSV early phaseHerpes simplex virus attachment and fusion

Inhibition of viral entry and fusion (e.g., docosanol) and inhibition of early viral enzymes such as DNA polymerase (e.g., acyclovir, foscarnet) or the helicase-primase complex (e.g., pritelivir) [1, 2, 4].