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Orthopoxvirus species and strain differences in cell entry
Zain Bengali1, P S Satheshkumar, Bernard Moss
1Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3210, USA.
Virology
|September 25, 2012
Summary
Orthopoxviruses, including vaccinia virus, utilize distinct cell entry mechanisms. Recent isolates favor endosomal entry, suggesting its biological significance, with viral determinants beyond A26/A25 influencing entry properties.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Vaccinia virus (VACV) exhibits variable cell entry pathways, including low pH endosomal routes and direct plasma membrane fusion.
- Previous studies identified strain-specific differences in VACV entry properties, influenced by factors like pH and specific inhibitors.
Purpose of the Study:
- To investigate the cell entry properties of recently isolated cowpox viruses and a monkeypox virus.
- To compare these properties with established VACV strains and identify viral determinants influencing entry mechanisms.
Main Methods:
- Analysis of cell entry pathways (low pH dependence, bafilomycin A1 sensitivity, heparin interaction) for multiple orthopoxvirus strains.
- Sequence comparisons, gene deletion, and gene swapping experiments to identify viral determinants.
Main Results:
- Recent orthopoxvirus isolates showed entry properties more similar to the WR strain of VACV, favoring endosomal entry.
- These findings highlight the biological importance of endosomal entry for orthopoxviruses.
- Viral determinants, potentially beyond the A26 and A25 proteins, were implicated in modulating virus entry.
Conclusions:
- Endosomal entry is a biologically significant pathway for orthopoxviruses.
- Multiple viral factors, not solely A26/A25 proteins, govern the distinct cell entry strategies observed in orthopoxviruses.
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