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Method for Measurement of Viral Fusion Kinetics at the Single Particle Level
14:59

Method for Measurement of Viral Fusion Kinetics at the Single Particle Level

Published on: September 7, 2009

Human cytomegalovirus penetrates host cells by pH-independent fusion at the cell surface

T Compton1, R R Nepomuceno, D M Nowlin

  • 1Department of Immunology, Scripps Research Institute, La Jolla, California 92037.

Virology
|November 1, 1992
PubMed

Insights

Human cytomegalovirus (HCMV) enters host cells through direct fusion of its envelope with the plasma membrane. This pH-independent entry mechanism bypasses endosomal pathways, initiating infection effectively.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Human cytomegalovirus (HCMV) is a significant human pathogen.
  • Understanding HCMV entry mechanisms is crucial for developing antiviral strategies.

Purpose of the Study:

  • To elucidate the precise mechanism of HCMV entry into host cells.
  • To determine whether HCMV entry occurs via pH-dependent endocytosis or direct plasma membrane fusion.

Main Methods:

  • Biochemical, genetic, and morphological analyses were employed.
  • Experiments utilized permissive fibroblasts and nonpermissive Chinese hamster ovary (CHO) cells.
  • Electron microscopy was used to visualize viral entry processes.

Main Results:

  • HCMV entry was demonstrated to be pH-independent, occurring at the plasma membrane.
  • Viral infectivity and immediate early (IE) gene expression were not affected by endocytosis inhibitors or agents altering endosomal pH.
  • A mutant CHO cell line defective in endosomal acidification supported IE gene expression.
  • Electron microscopy showed direct virion-plasma membrane fusion, with no evidence of endosomal uptake.

Conclusions:

  • HCMV utilizes a pH-independent fusion mechanism with the host cell plasma membrane for entry.
  • This direct fusion pathway allows HCMV to bypass endosomal compartments to initiate infection.

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