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Cell surface proteoglycans are not essential for infection by pseudorabies virus
A Karger1, A Saalmüller, F Tufaro
1Institute of Molecular and Cellular Virology, Friedrich Loeffler Institutes, Federal Research Centre for Virus Diseases of Animals, Germany.
Journal of Virology
|June 1, 1995
Summary
Pseudorabies virus (PrV) uses glycoprotein gC for initial cell attachment via heparan sulfate. However, PrV can infect cells even without gC, indicating a proteoglycan-independent attachment pathway.
Area of Science:
- Virology
- Cell Biology
- Glycobiology
Background:
- Herpesviruses, including pseudorabies virus (PrV), utilize cell surface proteoglycans, particularly heparan sulfate glycosaminoglycans, for initial attachment to host cells.
- In PrV, glycoprotein gC is identified as the primary heparan sulfate-binding protein on the viral envelope.
- The nonessential nature of PrV gC for infectivity raises questions about the necessity of proteoglycan interactions or the potential for alternative binding mechanisms.
Purpose of the Study:
- To investigate the role of glycoprotein gC and cellular proteoglycans in the attachment and infectivity of pseudorabies virus (PrV).
- To determine if alternative viral envelope proteins can mediate heparan sulfate binding in the absence of gC.
- To elucidate the mechanisms of PrV attachment and entry into target cells, particularly the existence of proteoglycan-independent pathways.
Main Methods:
- Infectivity assays using isogenic gC-positive (gC+) and gC-negative (gC-) PrV strains on mouse L-cell derivatives with impaired glycosaminoglycan biosynthesis.
- Utilized a fluorescence-based beta-galactosidase assay and fluorescence-activated cell sorting (FACS) for sensitive detection and quantification of viral infection at the single-cell level.
- Attachment studies employing radiolabeled PrV virions, with or without gC or the essential gD, to assess binding to cell surface components.
Main Results:
- Glycoprotein gC was confirmed as the sole proteoglycan-binding envelope protein in the PrV virion.
- Cellular proteoglycans were found to be non-essential for the infectivity of PrV.
- Pseudorabies virus gD primarily mediates binding to non-proteoglycan cell surface components, highlighting a proteoglycan-independent attachment mechanism for PrV entry.
Conclusions:
- Pseudorabies virus (PrV) possesses a functional proteoglycan-independent attachment and entry mechanism into target cells.
- While glycoprotein gC binds to heparan sulfate, this interaction is not essential for PrV infection, suggesting alternative viral attachment strategies.
- The findings reveal a dual mode of PrV cell attachment, involving both proteoglycan-dependent and independent pathways, with gD playing a role in the latter.