A Virus Genetic System to Analyze the Fusogenicity of Human Cytomegalovirus Glycoprotein B Variants

Viruses. 2023 Apr 16;15(4):979. doi: 10.3390/v15040979.


Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce the fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

Keywords: UL55; cell–cell fusion; entry; glycoprotein B; human herpesvirus 5; infectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cytomegalovirus*
  • Humans
  • Viral Envelope Proteins* / metabolism
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / metabolism
  • Virus Internalization


  • glycoprotein B, Simplexvirus
  • Viral Envelope Proteins
  • Viral Fusion Proteins

Grants and funding

This research was funded by the Deutsche Forschungsgemeinschaft KFO296, projects BR1730/7-1 and BR1730/9-1 (to W.B.) X.Z. was supported by a scholarship from the China Scholarship Council (No. 202008080174).