The Neuropathic Itch Caused by Pseudorabies Virus

Abstract

Pseudorabies virus (PRV) is an alphaherpesvirus related to varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV1). PRV is the causative agent of Aujeskzy’s disease in swine. PRV infects mucosal epithelium and the peripheral nervous system (PNS) of its host where it can establish a quiescent, latent infection. While the natural host of PRV is the swine, a broad spectrum of mammals, including rodents, cats, dogs, and cattle can be infected. Since the nineteenth century, PRV infection is known to cause a severe acute neuropathy, the so called “mad itch” in non-natural hosts, but surprisingly not in swine. In the past, most scientific efforts have been directed to eradicating PRV from pig farms by the use of effective marker vaccines, but little attention has been given to the processes leading to the mad itch. The main objective of this review is to provide state-of-the-art information on the mechanisms governing PRV-induced neuropathic itch in non-natural hosts. We highlight similarities and key differences in the pathogenesis of PRV infections between non-natural hosts and pigs that might explain their distinctive clinical outcomes. Current knowledge on the neurobiology and possible explanations for the unstoppable itch experienced by PRV-infected animals is also reviewed. We summarize recent findings concerning PRV-induced neuroinflammatory responses in mice and address the relevance of this animal model to study other alphaherpesvirus-induced neuropathies, such as those observed for VZV infection.

First Report of a Severe Outbreak of Aujeszky’s Disease in Cattle in Sicily (Italy)

“…The confirmation of AD was made based on the real-time PCR and immunohistochemical results. The symptoms described in the present study were similar to those reported in the literature in cattle and were mainly characterized by neuropathic itch, considered a typical sign of AD in non-natural hosts [ 8 , 17 , 20 , 21 , 22 , 33 ]. Although the presence of itching may facilitate the diagnosis of AD, a differential diagnosis is required for psoroptic and sarcoptic mange and pediculosis.…”

Severe Outbreak of Aujeszky’s Disease in Cattle in Nebrodi Park Area (Sicily)

“…The confirmation of AD was made on the basis of the real time PCR and immunohistochemical results. The symptoms described in the present study were similar to those reported in literature in cattle and were mainly characterized by neuropathic itch, considered a typical sign of AD in non-natural hosts (Hutchcroft T. 1975;Hargemoser W.A et al1978;Matsuoka et al 1987;Anusuz Z. et al 1992;Fukusho A et al 1998;Laval and Enquist, 2020). Although the presence of itching may facilitate the diagnosis of AD, a differential diagnosis is required for psoroptic and sarcoptic mange, pediculosis .…”

“…In case of virus exposure through the oral, rectal and vaginal mucosa, pruritus typically develops in head, shoulder, flank, hind quarters and perineum (Hutchcroft T 1975;Hopp W. et al 1985), whereas, head and neck are mainly involved when infection occurs trough the nasal mucosa or respiratory tract (Down C. 1962;Hopp W. et al 1985.). The differential location of pruritus and pathological findings, suggest different distribution of the virus (Laval and Enquist, 2020). The pruritus indeed usually develops at the point of inoculation of the virus, reaching the related segment of the spinal cord from peripheric nerve termination.…”

Intestinal Viral Loads and Inactivation Kinetics of Livestock Viruses Relevant for Natural Casing Production: A Systematic Review and Meta-Analysis

“…New born and nursing pigs are most severely affected showing mortality rates of 100% and 50%, respectively. Respiratory and neurological signs (mad itch) in weaned pigs and abortions in pregnant sows are hallmarks of this disease [ 78 , 79 , 80 ]. Eradication of PrV in large parts of the world was feasible due to efficacious marker vaccines in combination with accurate differential diagnostic tools [ 81 ].…”