Pseudorabies

Pseudorabies is a viral disease in swine that is endemic in most parts of the world. It is caused by Suid herpesvirus 1 (SuHV-1), which is also called Pseudorabies virus (PRV) and is also known as Aujeszky's disease, and in cattle as mad itch. PRV is considered to be the most economically important viral disease of swine in areas where hog cholera has been eradicated. Other domestic and wild mammals, such as cattle, sheep, goats, cats, dogs, and raccoons, are also susceptible. The disease is usually fatal in these hosts.

Research on PRV in pigs has pioneered animal disease control with genetically modified vaccines. PRV is now extensively studied as a model for basic processes during lytic herpesvirus infection, and for unravelling molecular mechanisms of herpesvirus neurotropism.

Although the word "pseudorabies" means "false rabies," or "rabies-like," it is a misnomer. Pseudorabies is related to the herpes virus, not the rabies virus.

History
The earliest reports of a disease suspected to be pseudorabies were in 1813 in the United States. These reports described a condition in cattle characterized by severe itching and called mad itch. In 1902 a Hungarian veterinarian, Aladár Aujeszky, isolated PRV from a dog, ox, and cat and showed that it caused the same disease in swine and rabbits. The name pseudorabies came from the symptoms similar to rabies that it caused in rabbits.

Disease overview
The virus is shed in the saliva and nasal secretions of infected swine and is spread through oral or nasal contact. Aerosolization of the virus and transmission by fomites also may occur. The virus may potentially survive for seven hours in humid air and spread up to two kilometers. Furthermore, it may survive on well water for up to seven hours, in green grass, soil, and feces for up to two days, in contaminated feed for up to three days, and in straw bedding for up to four days.

Diagnosis is made through an ELISA test. Vaccines are available for swine (ATCvet codes: inactivated,  live, plus various combinations). There are eradication programs in the United States and the United Kingdom. In 2004 the commercial swine population of the United States was declared free of pseudorabies, but the disease remained in feral pig populations.

Symptoms
Swine are usually asymptomatic, but PRV can cause abortion, high mortality in piglets, and coughing, sneezing, fever, constipation, depression, seizures, ataxia, circling, and excess salivation in piglets and mature pigs. Mortality in piglets less than one month of age is close to 100 percent, but it is less than 10 percent in pigs between one and six months of age. Pregnant swine can reabsorb their litters; deliver mummified, stillborn, or weakened piglets. In cattle, symptoms include intense itching followed by neurological signs and death. In dogs, symptoms include intense itching, jaw and pharyngeal paralysis, howling, and death. In cats, the disease is so rapidly fatal that there are usually no symptoms. Any infected secondary host generally only lives two to three days.

Species
Populations of wild boar, or feral hogs (Sus scrofa), in the U.S. commonly contract and spread the virus throughout their range. Mortality is highest in young piglets. Pregnant sows often abort when infected. Otherwise healthy male adults (boars) are typically latent carriers, that is, they harbor and transmit the virus without displaying symptoms or suffering disability.

Swine (both domestic and feral) are usual reservoirs for this virus, though it does affect other species, often with high mortality. Pseudorabies has been reported in other mammals, including brown bears, and black bears, Florida panther, raccoons, coyotes, and whitetail deer. In most cases, contact with pigs or pig products was either known or suspected. Outbreaks in farm fur species in Europe (mink and foxes) have been associated with feeding infected pig products. Many other species can be experimentally infected. Humans are not potential hosts.

Transmission
Pseudorabies is highly contagious. In most cases, this disease is transmitted through nose-to-nose contact. Nose-to-nose contact is the most common type of transmission because Pseudorabies is mostly present in nasal and oral areas. This disease can wipe out entire herds.

Prevention
Although there is no specific treatment for acute infection with pseudorabies virus, vaccination can alleviate clinical signs in pigs of certain ages. Typically, mass vaccination of all pigs on the farm with a modified live virus vaccine is recommended. Intranasal vaccination of sows and neonatal piglets 1-7 days old, followed by IM vaccination of all other swine on the premises, helps reduce viral shedding and improve survival. The modified live virus replicates at the site of injection and in regional lymph nodes. Vaccine virus is shed in such low levels that mucous transmission to other animals is minimal. In gene-deleted vaccines, the thymidine kinase gene has also been deleted; thus, the virus cannot infect and replicate in neurons. It is recommended that breeding herds be vaccinated quarterly, and that finisher pigs be vaccinated after levels of maternal antibody decrease. Regular vaccination results in excellent control of the disease. Concurrent antibiotic therapy via feed and IM injection is recommended for controlling secondary bacterial pathogens.

Applications in Neuroscience
PRV is a powerful tool used in neurobiology that can be employed to analyze neural circuits in the central nervous system (CNS). The Bartha strain of PRV is an attenuated form developed in 1961, and is employed as a retrograde transneuronal tracer. PRV-Bartha is transported to a neuronal cell body via its axon where it is replicated and dispersed throughout the cytoplasm and the dendritic tree. PRV-Bartha is able to cross synaptic gaps into the axons of only synaptically connected neurons, thereby propagating the virus in the retrograde fashion. Using temporal studies and/or genetically engineered strains of PRV-Bartha, second, third, and higher order neurons may be identified in the neural network of interest.