Title: Pseudorabies

{{Short description|Species of virus}}
{{Distinguish|rabies|rabies virus}}
{{Virusbox
| name = Pseudorabies virus
| parent = Varicellovirus 
| species = Varicellovirus suidalpha1
| synonyms = 
* Suid alphaherpesvirus 1
* Suid herpesvirus 1
* Pseudorabies virus
| synonyms_ref = &lt;ref&gt;{{cite web|url=https://ictv.global/taxonomy/taxondetails?taxnode_id=202301456&amp;taxon_name=Varicellovirus%20suidalpha1|title=History of the taxon: Species: ''Varicellovirus suidalpha1'' (2023 Release, MSL #39)|author=&lt;!--Not stated--&gt;|date=|website=ictv.global|publisher=International Committee on Taxonomy of Viruses|access-date=29 January 2025|quote=}}&lt;/ref&gt;
}}

'''Aujeszky's disease''', usually called '''pseudorabies''' in the [[United States]], is a [[virus|viral]] disease in [[pig|swine]] that is [[endemic (epidemiology)|endemic]] in most parts of the world. It is caused by '''pseudorabies virus''' ('''PRV'''). Aujeszky's disease is considered to be the most economically important viral disease of swine in areas where classical swine fever ([[hog cholera]]) has been eradicated.&lt;ref name=Fenner_1993&gt;{{cite book|author1=Fenner, Frank J. |author2=Gibbs, E. Paul J. |author3=Murphy, Frederick A. |author4=Rott, Rudolph |author5=Studdert, Michael J. |author6=White, David O. |title=Veterinary Virology (2nd ed.)|publisher=Academic Press, Inc|year=1993|isbn=978-0-12-253056-2}}&lt;/ref&gt; Other [[mammal]]s, such as [[cattle]], [[sheep]], [[goat]]s, [[cat]]s, [[dog]]s, and [[raccoon]]s, are also susceptible. The disease is usually fatal in these animal species.

Research on PRV in pigs has pioneered animal disease control with genetically modified vaccines. PRV is now used in model studies of basic processes during lytic herpesvirus infection, and for unravelling molecular mechanisms of herpesvirus [[neurotropism]].&lt;ref name=sobrino9&gt;{{cite book|chapter-url=http://www.horizonpress.com/avir|author=Mettenleiter|year=2008|chapter=Molecular Biology of Animal Herpesviruses|title=Animal Viruses: Molecular Biology|publisher=Caister Academic Press|isbn=978-1-904455-22-6}}&lt;/ref&gt;&lt;ref name=Sandri&gt;{{cite book |editor-last = Sandri-Goldin |editor-first=RM | title = Alpha Herpesviruses: Molecular and Cellular Biology| publisher = Caister Academic Press| year = 2006| url=http://www.horizonpress.com/ahv|isbn = 978-1-904455-09-7}}&lt;/ref&gt;

== History ==
In 1902, a [[Hungary|Hungarian]] [[veterinarian]], [[Aladár Aujeszky]], demonstrated a new infectious agent in a dog, ox, and cat, and showed it caused the same disease in swine and [[rabbit]]s. In the following decades the infection was found in several European countries, especially in cattle, where local intense [[pruritus]] (itching) is a characteristic symptom. In the United States, a well known disease in cattle called &quot;mad itch&quot; was concluded to be in fact Aujeszky's disease.&lt;ref&gt;{{cite journal|vauthors=Pomeranz L, Reynolds A, Hengartner C |title=Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine|journal=Microbiol Mol Biol Rev|volume=69|issue=3|pages=462–500|year=2005|pmid=16148307|doi=10.1128/MMBR.69.3.462-500.2005|pmc=1197806}}&lt;/ref&gt;

== Disease overview ==
[[Image:Pseudorabies in Wild Swine, distribution in USA.svg|thumb|250px|Wild pigs [[Seropositivity|seropositive]] for pseudorabies in the United States&lt;br/&gt;{{Color box|#c0b410|border=darkgray}} Present&lt;br/&gt;{{Color box|#21ab21|border=darkgray}} Absent]]

The virus is shed in the saliva and nasal secretions of swine infected by the respiratory route. [[Aerosol]]ization of the virus and transmission by [[fomite]]s also may occur. The virus may potentially survive for seven hours in humid air, and 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.&lt;ref name=Merck&gt;{{cite web| title = Pseudorabies: Introduction| work = The Merck Veterinary Manual| year = 2006| url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/102200.htm| access-date = 2007-03-31}}&lt;/ref&gt;

Diagnosis is made mainly by virus isolation in tissue cultures, or through [[ELISA]] or PCR tests. Vaccines are available for swine ([[ATCvet]] codes: {{ATCvet|I09|AA01}} inactivated, {{ATCvet|I09|AD01}} live, plus various combinations).&lt;ref&gt;{{cite journal|vauthors=Pensaert M, Labarque G, Favoreel H, Nauwynck H |title=Aujeszky's disease vaccination and differentiation of vaccinated from infected pigs|journal=Dev Biol (Basel)|volume=119|pages=243–54|year=2004|pmid=15742635}}&lt;/ref&gt; The infection has been eradicated in a number of European countries. In the United States, the domestic swine population in 2004 was declared free of Aujeszky's disease, though the infection still remains in feral pig populations.&lt;ref&gt;{{cite web| last = Amass| first = S.F.| title = Exotic Diseases: Are you Prepared? Are you Ready?| work = Proceedings of the North American Veterinary Conference| year = 2006| url = http://www.ivis.org/proceedings/navc/2006/LA/119.asp| access-date = 2007-03-31}}&lt;/ref&gt;

== Clinical signs ==
Respiratory infection is usually asymptomatic in pigs more than two months old, but it 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%, but it is less than 10% in pigs between one and six months of age. Pregnant swine can reabsorb their litters or deliver mummified, stillborn, or weakened piglets.&lt;ref name=Carter&gt;{{cite web |author=Carter, G.R. |author2=Flores, E.F. |author3=Wise, D.J.|year=2006|title=Herpesviridae|work=A Concise Review of Veterinary Virology| url=http://www.ivis.org/advances/Carter/Part2Chap11/chapter.asp?LA=1 |url-access=registration |access-date=2006-06-04}}&lt;/ref&gt; In cattle, symptoms include intense itching followed by neurological signs and death. In dogs, symptoms include intense itching, jaw and [[Pharynx|pharyngeal]] paralysis, howling, and death.&lt;ref name=Fenner_1993/&gt; Any infected secondary host generally only lives two to three days.&lt;ref name=Merck/&gt;

Genital infection appears to have been common in a great part of the 20th century in many European countries in swine herds, where boars from boar centres were used for natural service of sows or gilts. This disease manifestation has always been asymptomatic in affected pigs, and presence of the infection on a farm was detected only because of cases in cattle showing pruritus on the hindquarters.&lt;ref&gt;Bitsch, Viggo (2015). ''[http://suhv1epidemiology.blogspot.com/ Principal Epidemiological Features of Aujeszky's Disease in Swine and Cattle]''. {{ISBN|978-87-994685-1-5}}.&lt;/ref&gt;

In susceptible animals other than swine, infection is usually fatal, and the affected animals most often show intense pruritus in a skin area. Pruritus in Aujeszky's disease is considered a phantom sensation as virus has never been found at the site of pruritus.&lt;ref name=&quot;Bitsch, Viggo 2015&quot;&gt;Bitsch, Viggo (2015)&lt;/ref&gt;

== Pathogenicity and virulence of PRV ==
{{More citations needed section|reason=The only citation is a broken-link one made by a user citing something they apparently wrote themself|date=January 2021}}

The epidemiology of Aujeszky's disease varies with the pathogenicity or virulence of the virus strain involved. This is best illustrated by the development of the severity of the disease in Denmark, where import of swine had been forbidden for decades up to 1972. Before 1964 only genital strains were spread, but then respiratory strains appeared, which subsequently were spread rapidly over the country, mainly by the trade of animals. In the late 1970s more virulent strains developed. The disease in swine became much more severe, outbreaks of respiratory disease in cattle rose dramatically, and the infection was spread airborne to other swine herds. The higher virulence of these virus strains was associated with a certain ability to create syncytia (cell fusion) in tissue cultures (syncytial virus strains). Comprehensive restriction fragment pattern analyses of virus DNA have documented that the more virulent strains had not been introduced from abroad but had developed in two steps from the original Danish strains. The correlation between high virulence of virus strains and syncytium formation in tissue cultures was confirmed by examinations of isolates from other countries. This second step in the severity development of the disease in Denmark caused the decision to eradicate. New outbreaks after the eradication of the indigenous infection by the end of 1985 were all caused by foreign highly virulent, syncytial strains introduced by airborne transmission from Germany.&lt;ref name=&quot;Bitsch, Viggo 2015&quot;/&gt;

Briefly, PRV is spread either genitally or respiratorily. Genital strains have been found to be non-syncytial. Respiratory strains may be of relatively low or of high virulence. In Europe, syncytial strains have been found to be highly virulent.

== Epidemiology ==
Populations of [[wild boar]], or feral hogs (''Sus scrofa''), in the US 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 signs or experiencing disability.&lt;ref&gt;Berryman Institute: [http://www.berrymaninstitute.org/pdf/managing-feral-pigs.pdf Managing Wild Pigs] {{webarchive|url=https://web.archive.org/web/20110905100520/http://www.berrymaninstitute.org/pdf/managing-feral-pigs.pdf |date=2011-09-05 }}&lt;/ref&gt;

Swine (both domestic and feral) are usual reservoirs for this virus, though it does affect other species. Aujeszky's disease has been reported in other mammals, including brown bears, and [[American black bear|black bears]], [[Florida panther]]s, [[raccoon]]s, [[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 [[fox]]es) have been associated with feeding contaminated pig products. Many other species can be experimentally infected. Humans are not potential hosts.&lt;ref&gt;[http://www.evira.fi/portal/fi/elaimet/elainten_terveys_ja_elaintaudit/elaintaudit/usealle_elainlajille_yhteiset_taudit/aujeszkyn_tauti/ Finnish Food Safety Authority Evira: Aujeszkyn tauti (AD, pseudorabies)] {{webarchive|url=https://web.archive.org/web/20110717025719/http://www.evira.fi/portal/fi/elaimet/elainten_terveys_ja_elaintaudit/elaintaudit/usealle_elainlajille_yhteiset_taudit/aujeszkyn_tauti/ |date=2011-07-17 }}&amp;nbsp;{{in lang|fi}}&lt;/ref&gt;

Cattle have been found to be infected either by the respiratory or the vaginal route ([[iatrogenic]] cases disregarded). Primary infection of mucous membranes of the upper respiratory tract is associated with head pruritus, while lung infection results in chest pruritus. Vaginal infection of bovines, which regularly show pruritus of the hindquarters, has been found to be associated with a concurrent genital infection in swine on the same premises, and investigations have evidenced that the vaginal infection of cattle had been sexually transmitted by man from infected sows.{{Citation needed|date=May 2020}} Genital infection in swine herds has been closely correlated with the use of boars from boar centres for natural service of sows.&lt;ref name=&quot;Bitsch, Viggo 2015&quot;/&gt;

== Transmission ==
Aujeszky's disease is highly contagious. The infection is commonly considered to be transmitted among swine through nose-to-nose contact, because the virus is mostly present in nasal and oral areas. This notion, however, is contradicted by results from epidemiological studies, according to which the decisive spread within herds occurs by air currents over many meters. Correspondingly, the risk of airborne transmission of highly virulent virus strains from acutely infected herds to other swine herds has been found to be very high. The infection has been found transmitted over distances of many kilometers.&lt;ref name=&quot;Bitsch, Viggo 2015&quot;/&gt;
Otherwise, the infection is most often transmitted into herds by introduction of acutely or latently infected pigs.
Concerning transmission to cattle, see section above.

== Prevention ==
Although no specific treatment for acute infection with PRV is available, 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 one to seven days old, followed by intramuscular (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, 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. Breeding herds are recommended to be vaccinated quarterly, and finisher pigs should 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.&lt;ref&gt;{{Cite web | url=http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/102200.htm | title=Merck Veterinary Manual}}&lt;/ref&gt;

== Applications in neuroscience ==
PRV can be used to analyze neural circuits in the [[central nervous system]] (CNS). For this purpose the attenuated (less virulent) Bartha PRV strain is commonly used&lt;ref&gt;{{cite journal | author = Bartha A | year = 1961 | title = Experimental reduction of virulence of Aujesky's disease virus | journal = Magyar Allatorvosok Lapja | volume = 16 | pages = 42–45 }}&lt;/ref&gt; and is employed as a retrograde&lt;ref&gt;{{cite journal| title=Efficient retrograde transport of pseudorabies virus within neurons requires local protein synthesis in axons |vauthors=Koyuncu OO, Perlman DH, Enquist LW | journal=Cell Host Microbe |date=Jan 16, 2013 |volume=13 | issue=1 | pages=54–66| pmid = 23332155 | doi=10.1016/j.chom.2012.10.021 | pmc=3552305}}&lt;/ref&gt; and anterograde&lt;ref&gt;{{cite journal| title=Role of us9 phosphorylation in axonal sorting and anterograde transport of pseudorabies virus |vauthors=Kratchmarov R, Taylor MP, Enquist LW | journal=PLOS ONE |year= 2013 |volume=8 |issue=3 |article-number=e58776 | pmid= 23527020 | doi=10.1371/journal.pone.0058776 | pmc=3602541|bibcode=2013PLoSO...858776K |doi-access=free }}&lt;/ref&gt; [[viral neuronal tracing|transneuronal tracer]]. In the retrograde direction, 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 released at the synapse is able to cross the synapse to infect the axon terminals of synaptically connected neurons, thereby propagating the virus; however, the extent to which non-synaptic transneuronal transport may also occur is uncertain. 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.

== See also ==
{{Portal|Viruses}}
* [[Animal virology|Animal viruses]]
* [[Virology]]

== References ==
{{Reflist|2}}

== External links ==
{{Commons category}}
* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1197806/?tool=pubmed Overview of the virus and its applications in neuroscience]
* [http://www.horizonpress.com/gateway/animal-viruses.html Animal viruses]

{{Herpesvirales}}
{{Taxonbar|from=Q24808720|from2=Q17504621}}
{{Authority control}}

[[Category:Swine diseases]]
[[Category:Dog diseases]]
[[Category:Animal viral diseases]]
[[Category:Herpesviridae]]