Herpes Simplex Virus Glycoprotein C Regulates Low-pH Entry
| Autor: | Seth M. Schneider, Darin J. Weed, Suzanne M. Pritchard, Anthony V. Nicola, Tri Komala Sari, Katrina A. Gianopulos |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Conformational change
herpesviruses Endosome viruses lcsh:QR1-502 Herpesvirus 1 Human medicine.disease_cause Endocytosis Microbiology lcsh:Microbiology Host-Microbe Biology 03 medical and health sciences Protein Domains Viral Envelope Proteins Viral entry Chlorocebus aethiops medicine Animals Humans Molecular Biology Vero Cells 030304 developmental biology chemistry.chemical_classification 0303 health sciences 030306 microbiology Lipid bilayer fusion Herpes Simplex Hydrogen-Ion Concentration Virus Internalization herpes simplex virus Fusion protein QR1-502 3. Good health Cell biology Herpes simplex virus chemistry viral entry Glycoprotein viral glycoproteins Research Article |
| Zdroj: | mSphere, Vol 5, Iss 1, p e00826-19 (2020) mSphere mSphere, Vol 5, Iss 1 (2020) |
| ISSN: | 2379-5042 |
| Popis: | Herpesviruses are ubiquitous pathogens that cause lifelong latent infections and that are characterized by multiple entry pathways. We propose that herpes simplex virus (HSV) gC plays a selective role in modulating HSV entry, such as entry into epithelial cells, by a low-pH pathway. gC facilitates a conformational change of the main fusogen gB, a class III fusion protein. We propose a model whereby gC functions with gB, gD, and gH/gL to allow low-pH entry. In the absence of gC, HSV entry occurs at a lower pH, coincident with trafficking to a lower pH compartment where gB changes occur at more acidic pHs. This report identifies a new function for gC and provides novel insight into the complex mechanism of HSV entry and fusion. Herpes simplex viruses (HSVs) cause significant morbidity and mortality in humans worldwide. Herpesviruses mediate entry by a multicomponent virus-encoded machinery. Herpesviruses enter cells by endosomal low-pH and pH-neutral mechanisms in a cell-specific manner. HSV mediates cell entry via the envelope glycoproteins gB and gD and the heterodimer gH/gL regardless of pH or endocytosis requirements. Specifics concerning HSV envelope proteins that function selectively in a given entry pathway have been elusive. Here, we demonstrate that gC regulates cell entry and infection by a low-pH pathway. Conformational changes in the core herpesviral fusogen gB are critical for membrane fusion. The presence of gC conferred a higher pH threshold for acid-induced antigenic changes in gB. Thus, gC may selectively facilitate low-pH entry by regulating conformational changes in the fusion protein gB. We propose that gC modulates the HSV fusion machinery during entry into pathophysiologically relevant cells, such as human epidermal keratinocytes. IMPORTANCE Herpesviruses are ubiquitous pathogens that cause lifelong latent infections and that are characterized by multiple entry pathways. We propose that herpes simplex virus (HSV) gC plays a selective role in modulating HSV entry, such as entry into epithelial cells, by a low-pH pathway. gC facilitates a conformational change of the main fusogen gB, a class III fusion protein. We propose a model whereby gC functions with gB, gD, and gH/gL to allow low-pH entry. In the absence of gC, HSV entry occurs at a lower pH, coincident with trafficking to a lower pH compartment where gB changes occur at more acidic pHs. This report identifies a new function for gC and provides novel insight into the complex mechanism of HSV entry and fusion. |
| Databáze: | OpenAIRE |
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