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Updated: Jun 28, 2026
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Temporal Analysis of the Nuclear-to-cytoplasmic Translocation of a Herpes Simplex Virus 1 Protein by Immunofluorescent Confocal Microscopy
Published on: November 4, 2018
Structure-function analysis of herpes simplex virus glycoprotein B with fusion-from-without activity
Devin G Roller1, Stephen J Dollery, James L Doyle
1Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0678, USA.
Virology
|October 28, 2008
Summary
Herpes simplex virus (HSV) glycoprotein B (gB) mutations enable fusion-from-without (FFWO), rapidly inducing cell fusion. This FFWO activity correlates with receptor usage but doesn't alter HSV entry pathways.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Fusion-from-without (FFWO) is a process where virions induce cell fusion without viral protein synthesis.
- Specific mutations in herpes simplex virus (HSV) envelope glycoprotein B (gB) can confer FFWO activity to wild-type HSV.
- Understanding the mechanisms of HSV entry and fusion is crucial for developing antiviral strategies.
Purpose of the Study:
- To analyze the entry and cell fusion phenotypes of HSV with FFWO-competent gB.
- To investigate the relationship between FFWO activity, cellular receptors (nectin-1, nectin-2, HVEM), and viral entry pathways.
- To determine if FFWO gB alters the global conformation, antigenic structure, or entry pathway selection of HSV.
Main Methods:
- Generation and phenotypic analysis of HSV strains with FFWO gB mutations.
- Assessment of viral entry and cell-cell fusion mediated by specific HSV receptors.
- Analysis of gB conformation using monoclonal antibodies.
- Inhibition studies using neutralizing antibodies against gB and gD.
Main Results:
- HSV with FFWO gB efficiently mediated FFWO via specific gD-receptors, correlating with viral entry efficiency via those receptors.
- FFWO gB did not switch HSV entry from a pH-dependent endocytic pathway to a direct, pH-independent fusion pathway.
- FFWO gB exhibited altered reactivity with certain monoclonal antibodies, suggesting changes in antigenic structure without global conformational alterations.
- FFWO was blocked by neutralizing antibodies to gB or gD.
Conclusions:
- The roles of gB in FFWO and virus-cell fusion during entry are related but distinct.
- FFWO function of gB is not a determinant for selecting HSV entry pathways.
- Antigenic differences in FFWO gB may be linked to its enhanced fusion activity.
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