Pseudorabies Virus

A 2020 research paper titled "A Novel Human Acute Encephalitis Caused by a Pseudorabies Virus Variant Strain" reported four cases of acute encephalitis in humans linked to infection with pseudorabies virus (PRV). The study summarized the clinical features of PRV infection in humans and, for the first time, successfully isolated a PRV strain—hSD-1/2019—from the cerebrospinal fluid of affected patients. This strain exhibited biological characteristics closely resembling those of the PRV variant strains currently circulating among China's pig populations. Importantly, this research provides the first direct and compelling virological evidence of the cross-species transmission of pseudorabies virus (PRV) from animals to humans.

Pseudorabies is an acute infectious disease primarily affecting livestock and various wild animals, caused by the Pseudorabies virus (PRV). Given its significant impact on China's animal husbandry industry and human health, China has classified pseudorabies as a Category II animal epidemic disease.

Pseudorabies virus belongs to the Herpesviridae family, specifically the Alphaherpesvirinae subfamily and Porcine herpesvirus 1, according to the biological classification system. While multiple animal species can be infected, pigs are the primary reservoir and main source of transmission for pseudorabies virus; thus, they are the key focus for prevention and control. Pigs can also infect other animals, including dogs, cats, horses, cattle, sheep, and various wild species. PRV is a highly neurotropic virus that can cause pigs to exhibit neurological symptoms ranging from mild to severe. The occurrence of pseudorabies disease largely depends on the age of the pig, as well as its active and passive immune status, the virulence of the specific viral strain involved, and the quantity of the virus present.

After the virus enters the body, it initially multiplies in the tonsils and pharyngeal mucosa. Within 24 hours, it can reach the spinal cord and brain via the olfactory nerve, trigeminal nerve, and swallowing nerve's perineural lymphatic pathways. (The virus can also travel through the bloodstream to various parts of the body, but in the blood, it appears intermittently at low titers, making it difficult to detect.)

PRV exhibits strong resistance to external factors, surviving for more than a month in contaminated pigsties and remaining viable in meat for over five weeks. The virus primarily spreads through direct contact, but it can also transmit via skin wounds and airborne routes. The main route of transmission is ingestion of feed or dead pork contaminated with the virus. Additionally, the virus can be passed between rats and pigs, while infected or deceased rats may serve as an infection source for dogs and cats.

After 6-7 days of infection, the sow's milk contains the virus for 3-5 days, and piglets can become infected by nursing. When pregnant sows are infected, vertical transmission often occurs, allowing the virus to invade the fetus. Infected breeding pigs and their offspring may shed the virus for an extended period, making this disease persistently widespread and extremely difficult to eradicate. Cattle, frequently exposed to pigs and rodents, often contract the disease—and once infected, nearly 100% of them succumb.

The younger the nursing piglets are in days of age, the higher their incidence and mortality rates; these rates decline as they grow older. After weaning, piglets typically no longer show symptoms of the disease but can still carry and shed the virus for an extended period.

Poor husbandry management, inadequate sanitation, ineffective control of other diseases, and various stress factors can all easily trigger this disease.

The clinical signs of infected pigs can vary depending on their age. Typically, piglets during the nursing period exhibit fever and acute encephalomyelitis, while adult pigs usually show either asymptomatic infections or respiratory symptoms. In pregnant sows, about 50% may experience abortion, stillbirths, and respiratory issues—but notably, they do not display intense itching. Meanwhile, infection in other animal species often leads to a high mortality rate, with the most distinctive symptom being severe itching in specific areas of the body. Additionally, PRV can cause infertility in breeding pigs, primarily resulting in repeated failures to conceive in sows, with a return-to-estrus rate as high as 90%. In boars, symptoms include testicular swelling and atrophy, ultimately leading to a complete loss of reproductive capability.

Generally, there are no obvious characteristic pathological changes. The kidneys exhibit pinpoint hemorrhages, and in cases with neurological symptoms, the meninges show marked congestion, bleeding, and edema, accompanied by an increase in cerebrospinal fluid. Scattered white necrotic spots are observed in the tonsils, liver, and spleen. The lungs reveal pulmonary edema, along with lobular interstitial pneumonia or scattered hemorrhagic foci. Meanwhile, the gastric mucosa exhibits catarrhal inflammation, with submucosal bleeding at the gastric fundus. Histologically, the central nervous system predominantly displays diffuse non-purulent meningitis, characterized by prominent perivascular cuffs and glial cell necrosis. In addition, intranuclear eosinophilic inclusion bodies are found within nerve cells as well as in lymphocytes of the nasopharyngeal mucosa, spleen, and lymph nodes.

If animals are infected with PRV, particularly after viremia occurs, inflammation of the central nervous system often develops, leading to a range of neurological syndromes of varying severity. The primary manifestation is heightened skin sensitivity. Following inflammation of the brain and spinal cord, paralysis may occur in certain nerves—especially those innervating the tongue and pharynx. If the disease progresses over an extended period, it can subsequently trigger pathological changes in the respiratory and digestive organs. As a result, research not only focuses on the central nervous system but also extends to the respiratory and digestive systems.

Detection of pseudorabies virus can be performed using standardized ELISA kits or by IFA testing. PCR can also be employed for confirmatory diagnosis. In pigs, infection with this disease often follows a subclinical course; therefore, diagnosis relies primarily on serological methods, including serum neutralization tests, agar gel diffusion assays, and complement fixation tests. Among these, the serum neutralization test is the most sensitive and produces the fewest false-positive results, making it the officially recognized diagnostic method in certain countries. With the advent of genetically attenuated vaccines, clinical laboratories now have reagents available that can distinguish between vaccine strains and wild-type viruses.

Currently, there is no effective drug treatment for this disease; however, in emergency situations, high-immunity serum can be used to reduce the mortality rate.

Eliminating rodents is crucial for preventing this disease. Pigs are significant carriers of the virus, so cattle and pigs must be strictly kept in separate facilities. In addition, serum neutralization tests should be conducted on pig herds; any pigs testing positive must be isolated and culled. This quarantine process should be repeated every 3 to 4 weeks until both consecutive tests come back negative.

Using vaccines to immunize animals is one of the key strategies for controlling pseudorabies. Currently, commonly used vaccines include inactivated vaccines, attenuated live vaccines, and genetically modified marker vaccines. While inactivated vaccines are highly safe and do not cause viral shedding, they fail to elicit robust cellular immune responses, resulting in lower protective efficacy compared to attenuated live vaccines. Attenuated live vaccines, on the other hand, offer better protection but carry the risk of reversion to virulence, potentially triggering disease outbreaks—and they can also establish latent infections. Genetically modified marker vaccines primarily target deletions in genes such as gE, gC, gG, TK, and RR.

References

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2. Qingyun Liu, Xiaojuan Wang, Caihua Xie, et al., A novel human acute encephalitis caused by a pseudorabies virus variant strain [J]. Clinical Infectious Diseases 2020. ciaa987.

3. Liu Botao, Song Changjun, Liu Yizhong. Advances in the Study of Pathogenic Mechanisms of Pseudorabies Virus [J]. Journal of Northwest Minzu University (Natural Sciences Edition), 2008, 29(4):65-68.

4. Lu Chengping. Veterinary Microbiology (3rd ed.) [M]. Beijing: China Agricultural Press, 2005:474.

5. Chen Puyan. Veterinary Infectious Diseases (5th ed.) [M]. Beijing: China Agricultural Press, 2006:218-220.

6. Wenjun Ma, Kelly M. Lager, Juergen A. Richt, et al., Development of Real-Time

Polymerase Chain Reaction Assays for Rapid Detection and Differentiation of

Wild-Type Pseudorabies and Gene-Deleted Vaccine Viruses [J]. J Vet Diagn Invest 20:440–447 (2008).