Herpes simplex virus entry and uncoating process (HSV entry and uncoating) (HSV entry and uncoating)

The Herpes simplex virus (HSV) entry and uncoating process is a complex, multistep sequence essential for initiating infection and establishing lifelong latency. It begins with the attachment of the virus to host cell heparan sulfate proteoglycans, followed by the coordinated interaction of viral glycoproteins gB, gD, and the gH/gL complex with specific entry receptors such as nectin-1 and herpesvirus entry mediator (HVEM) [1.1.2, 1.1.3]. These interactions trigger the fusion of the viral envelope with the host cell membrane or endosomal membrane, releasing the nucleocapsid into the cytoplasm [1.1.2, 1.3.1]. The capsid is then transported to the nuclear pore complex, where the viral DNA is uncoated and injected into the nucleus to begin transcription [1.1.1, 1.5.4]. As a therapeutic target, this process offers a way to block infection before the viral genome can be established in the host, providing a prophylactic or early-intervention advantage over replication inhibitors [1.3.1, 1.3.2]. Drugs like docosanol target this stage by interfering with the fusion process, while experimental agents like neutralizing antibodies and small-molecule inhibitors aim to disrupt specific glycoprotein-receptor interfaces [1.2.1, 1.4.2]. Additionally, uncoating inhibitors like tromantadine have been developed to prevent the release of viral DNA from the capsid [1.2.1]. This target area is particularly relevant for treating acyclovir-resistant strains and reducing viral transmission [1.3.1, 1.3.3].

Other names

Viral entryViral uncoatingMembrane fusionViral adsorptionCapsid dockingDNA injectionn-Docosanol target

Inhibition of viral envelope fusion with the host cell membrane, blocking of viral glycoprotein interactions with host receptors (e.g., nectin-1, HVEM), and prevention of capsid docking or DNA release at the nuclear pore.