Propagation of pseudorabies virus in the nervous system of the mouse after intranasal inoculation
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N Babic1, T C Mettenleiter, G Ugolini
1Laboratoire de Génétique des Virus, C.N.R.S., 91198 Gif sur Yvette, France.
Abstract:
The propagation of pseudorabies virus (PrV) in the mouse nervous system was studied after intranasal inoculation of a PrV mutant expressing beta-galactosidase after insertion of the Escherichia coli Lac-Z gene into the gene encoding the nonstructural, nonessential glycoprotein gG. This allowed rapid detection of infected cells by a single step reaction with the substrate X-gal. The gG-beta-gal+ mutant behaved like the wild-type Kaplan strain of origin. The incubation period was very short and the animals did not survive more than 52 hr after inoculation. In the nasal cavity, the virus infected almost exclusively the respiratory epithelium. The virus propagated to the nervous system via three neuronal pathways: (i) the trigeminal route, with primary infection in the trigeminal ganglion followed by anterograde transneuronal transfer to the spinal trigeminal nucleus; (ii) the sympathetic route, with a first cycle of replication in the superior cervical ganglion and retrograde transneuronal transfer to sympathetic preganglionic neurons in the intermediolateral nucleus in the spinal cord; and (iii) the parasympathetic route, with primary infection in the pterygopalatine ganglion, followed by retrograde transneuronal transfer and replication in the superior salivatory nucleus. In contrast, the olfactory system was rarely found infected, probably because of the short survival of the animals.
Insights
Pseudorabies virus (PrV) rapidly infects mouse nervous systems via three distinct neuronal routes: trigeminal, sympathetic, and parasympathetic. This study tracked PrV propagation using a novel gG-beta-gal+ mutant for cell detection.
Area of Science:
- Virology
- Neuroscience
- Infectious Diseases
Background:
- Pseudorabies virus (PrV) is a significant pathogen.
- Understanding viral neuroinvasion is crucial for disease control.
- The nonstructural glycoprotein gG's role in PrV pathogenesis is not fully elucidated.
Purpose of the Study:
- To investigate the neuropropagation pathways of a pseudorabies virus (PrV) mutant in the mouse nervous system.
- To characterize the initial infection sites and neuronal routes following intranasal inoculation.
- To utilize a novel gG-beta-gal+ PrV mutant for efficient detection of infected cells.
Main Methods:
- Intranasal inoculation of mice with a PrV gG-beta-gal+ mutant.
- Detection of infected cells using X-gal substrate for beta-galactosidase activity.
- Histological analysis to trace viral spread through neuronal pathways.
Main Results:
- The gG-beta-gal+ mutant exhibited wild-type virulence, with a short incubation period and rapid mortality (≤52 hr).
- PrV primarily infected nasal respiratory epithelium.
- Three main neuronal routes of neuroinvasion were identified: trigeminal, sympathetic, and parasympathetic pathways.
- Olfactory system infection was minimal, likely due to the short survival time.
Conclusions:
- The study successfully mapped the neuroinvasive pathways of PrV in mice.
- The trigeminal, sympathetic, and parasympathetic routes are critical for PrV central nervous system entry.
- The gG-beta-gal+ mutant is a valuable tool for studying PrV neurotropism.