Herpes simplex virus 1 entry and fusion complex (HSV-1 entry machinery)

The Herpes simplex virus 1 (HSV-1) entry and fusion complex is a multi-component system essential for the virus to infect host cells [1, 3]. It comprises four viral glycoproteins—gB, gD, gH, and gL—and several host cell surface receptors, most notably Nectin-1, Herpesvirus entry mediator (HVEM), and 3-O-sulfated heparan sulfate [4, 5]. The entry process begins with the attachment of the virus to heparan sulfate proteoglycans, followed by the binding of viral gD to a host receptor [7, 12]. This binding event triggers a conformational change in gD that activates the gH/gL complex, which in turn signals the fusogen gB to mediate the fusion of the viral envelope with the host cell membrane [3, 10]. This complex is a primary target for antiviral research, as disrupting these interactions can block the initiation of infection and the spread of the virus between cells [2, 11]. Current therapeutic approaches include the use of docosanol, which stabilizes the host cell membrane to inhibit fusion, and experimental strategies such as peptide inhibitors and neutralizing antibodies that target specific glycoprotein-receptor interfaces [15, 17]. Understanding the structural basis of this machinery is crucial for developing next-generation antivirals that can overcome resistance to traditional DNA polymerase inhibitors [19, 20].

Other names

Host cell surface receptors for HSV-1 entry and membrane fusion machineryHSV-1 entry receptorsHSV-1 fusion machinerygB-gD-gH-gL complexHSV-1 entry complex

Inhibition of viral attachment to heparan sulfate, competitive inhibition of gD binding to host receptors (Nectin-1, HVEM), inhibition of gB-mediated membrane fusion, and stabilization of the host cell membrane to prevent viral entry.