Host cell glycoprotein processing pathways

Host cell glycoprotein processing pathways are essential cellular mechanisms located within the endoplasmic reticulum (ER) and Golgi apparatus that facilitate the post-translational modification of proteins. In the context of Herpes Simplex Virus (HSV) infection, the virus hijacks these host pathways to process its own envelope glycoproteins, such as gB, gD, and the gH/gL complex, which are critical for viral attachment, fusion, and egress (Source: PubMed, PMID: 16103208). Key enzymes in this pathway include alpha-glucosidase I and II, which remove terminal glucose residues from N-linked glycans to allow for proper protein folding via the calnexin/calreticulin cycle (Source: NIH, PMC3122611). Inhibition of these host enzymes by drugs like celgosivir or miglustat leads to the production of misfolded viral glycoproteins that are either degraded or non-functional, thereby preventing the maturation of infectious progeny (Source: PubChem). This host-directed approach is considered a broad-spectrum antiviral strategy that minimizes the risk of viral resistance because the virus cannot easily mutate to bypass a host-encoded requirement (Source: Wikipedia). However, because these pathways are also used for host protein synthesis, therapeutic use can be limited by off-target effects such as gastrointestinal distress and osmotic diarrhea (Source: StatPearls). Overall, targeting these pathways represents a strategy to disrupt the viral life cycle at the assembly and maturation stage.

Other names

N-linked glycosylation pathwayER-associated glycoprotein processingHost-mediated viral maturation

Inhibition of host alpha-glucosidases prevents the removal of terminal glucose residues from N-linked glycans on viral glycoproteins, leading to misfolding, ER-associated degradation, and the production of non-infectious viral particles.