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Pseudorabies virus envelope glycoprotein gI influences both neurotropism and virulence during infection of the rat
J P Card1, M E Whealy, A K Robbins
1Viral Diseases Research, Du Pont Merck Pharmaceutical Company, Wilmington, Delaware 19880-0228.
Abstract:
We previously demonstrated that intraocular injections of virulent and attenuated strains of pseudorabies virus (PRV) produce transneuronal infection of functionally distinct central visual circuits in the rat. The virulent Becker strain of PRV induces two temporally separated waves of infection that ultimately target all known retinorecipient neurons; the attenuated Bartha strain only infects a functionally distinct subset of these neurons. In this study, we demonstrate that deletion of a single viral gene encoding glycoprotein gI is sufficient to reproduce both the novel pattern of infectivity and the reduced neurovirulence of the Bartha strain of PRV. Glycoprotein gIII, a major viral membrane protein required for efficient adsorption of virus in cell culture, has no obvious role in determining the pattern of neuronal infectivity, but appears to function with gI to influence neurovirulence. These data suggest that neuroinvasiveness and virulence are the products of an interaction of viral envelope glycoproteins with as yet unidentified cellular receptors.
Insights
Pseudorabies virus (PRV) neurovirulence and infection patterns are determined by specific glycoproteins. Deleting the gI gene in PRV reduces neurovirulence and alters central visual circuit infection, similar to the Bartha strain.
Area of Science:
- Neuroscience
- Virology
- Molecular Biology
Background:
- Pseudorabies virus (PRV) strains exhibit differential neuroinvasiveness and infect distinct neuronal populations within the central visual circuits.
- Virulent PRV strains infect all retinorecipient neurons through temporally separated waves, while attenuated strains infect a subset.
Purpose of the Study:
- To investigate the role of specific pseudorabies virus (PRV) glycoproteins, particularly gI and gIII, in determining neurovirulence and the pattern of transneuronal infection in the central visual system.
- To elucidate the molecular mechanisms underlying PRV's neuroinvasiveness and virulence.
Main Methods:
- Intraocular injections of modified PRV strains (Becker and Bartha) and a gI deletion mutant in rats.
- Analysis of transneuronal viral spread within central visual circuits.
- Assessment of viral neurovirulence and infectivity patterns.
Main Results:
- Deletion of the glycoprotein gI gene in PRV is sufficient to replicate the attenuated Bartha strain's reduced neurovirulence and altered infectivity pattern.
- Glycoprotein gIII, while crucial for viral adsorption in vitro, does not significantly impact the pattern of neuronal infection.
- Glycoprotein gI and gIII appear to interact to influence PRV's neurovirulence.
Conclusions:
- Viral envelope glycoproteins, specifically gI, play a critical role in dictating the neuroinvasiveness and virulence of PRV.
- The interaction between viral glycoproteins and cellular receptors likely governs the specific pattern of neuronal infection and overall virulence.
- Understanding these glycoprotein functions provides insights into viral pathogenesis and potential therapeutic targets.