Virulent Pseudorabies Virus Infection Induces a Specific and Lethal Systemic Inflammatory Response in Mice

Area of Science:

• Virology
• Immunology
• Neuroscience

Background:

• Pseudorabies virus (PRV), an alphaherpesvirus, naturally infects swine but can cause severe, lethal neuropathy (
• mad itch
• ) in other mammals.
• The mechanisms underlying PRV-induced neuropathic itch and mortality remain unclear.
• Understanding the immune response is crucial for PRV infection outcomes.

Purpose of the Study:

• To investigate the pathophysiological and immunological processes of PRV infection in a nonnatural host.
• To elucidate the role of inflammation in PRV-induced neurotoxicity and lethality.
• To compare the effects of virulent (PRV-Becker) and attenuated (PRV-Bartha) PRV strains.

Main Methods:

• A mouse footpad inoculation model using PRV-Becker and PRV-Bartha strains.
• Histopathological analysis (hematoxylin and eosin staining) of infected tissues.
• Quantitative reverse transcription-PCR to measure PRV load.
• Measurement of plasma and tissue cytokine and chemokine levels (IL-6, G-CSF, Gro-1, MCP-1) and C-reactive protein.

Main Results:

• PRV-Becker infection induced severe pruritus, necrosis, neutrophil infiltration in footpads and dorsal root ganglia (DRGs), and mortality at 82 hpi.
• Elevated plasma levels of IL-6, G-CSF, and C-reactive protein indicated a systemic inflammatory response.
• PRV-Bartha infection did not cause pruritus or lethal systemic inflammation, despite replicating in the PNS and spreading to the brain.
• Significant IL-6 and G-CSF levels were detected in tissues of PRV-Becker infected mice.

Conclusions:

• A systemic inflammatory response, driven by cytokines like IL-6 and G-CSF, is critical for the severe pruritus and lethality of PRV-Becker infection in mice.
• PRV-Bartha, an attenuated strain, does not elicit this detrimental inflammatory response.
• These findings offer insights into PRV-induced neuroinflammation and highlight similarities with varicella-zoster virus (VZV) infections.