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Bovine alphaherpesvirus 1 (BoHV-1) is a virus of the family ''
Herpesviridae ''Orthoherpesviridae'', previously named and more widely known as ''Herpesviridae'', is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are commonly known as herp ...
'' and the subfamily ''
Alphaherpesvirinae ''Alphaherpesvirinae'' is a subfamily of viruses in the family ''Herpesviridae'', primarily distinguished by reproducing more quickly than other subfamilies in the ''Herpesviridae''. In animal virology the most important herpesviruses belong to ...
'', known to cause several diseases worldwide in
cattle Cattle (''Bos taurus'') are large, domesticated, bovid ungulates widely kept as livestock. They are prominent modern members of the subfamily Bovinae and the most widespread species of the genus '' Bos''. Mature female cattle are calle ...
, including rhinotracheitis,
vaginitis Vaginitis, also known as vulvovaginitis, is inflammation of the vagina and vulva. Symptoms may include itching, burning, pain, discharge, and a bad smell. Certain types of vaginitis may result in complications during pregnancy. The three mai ...
,
balanoposthitis Balanitis is inflammation of the glans penis. Balanoposthitis is the proper term when the foreskin is also affected. Balanitis on boys in diapers must be distinguished from redness caused by ammoniacal dermatitis. Etymology The word ''balanit ...
,
abortion Abortion is the early termination of a pregnancy by removal or expulsion of an embryo or fetus. Abortions that occur without intervention are known as miscarriages or "spontaneous abortions", and occur in roughly 30–40% of all pregnan ...
,
conjunctivitis Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...
, and
enteritis Enteritis is inflammation of the small intestine. It is most commonly caused by food or drink contaminated with pathogenic microbes,Dugdale, David C., IIII, and George F Longretc"Enteritis" MedlinePlus Medical Encyclopedia, 18 October 2008. Acces ...
. BoHV-1 is also a contributing factor in shipping fever, also known as bovine respiratory disease (BRD). It is spread horizontally through sexual contact,
artificial insemination Artificial insemination is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatment ...
, and aerosol transmission and it may also be transmitted vertically across the placenta. BoHV-1 can cause both clinical and subclinical infections, depending on the
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most cases, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its abili ...
of the strain. Although these symptoms are mainly non-life-threatening it is an economically important disease as infection may cause a drop in production and affect trade restrictions. Like other herpesviruses, BoHV-1 causes a lifelong latent infection and sporadic shedding of the virus. The
sciatic nerve The sciatic nerve, also called the ischiadic nerve, is a large nerve in humans and other vertebrate animals. It is the largest branch of the sacral plexus and runs alongside the hip joint and down the right lower limb. It is the longest and widest ...
and
trigeminal nerve In neuroanatomy, the trigeminal nerve (literal translation, lit. ''triplet'' nerve), also known as the fifth cranial nerve, cranial nerve V, or simply CN V, is a cranial nerve responsible for Sense, sensation in the face and motor functions ...
are the sites of latency. A reactivated latent carrier is normally the source of infection in a herd. The clinical signs displayed are dependent on the virulence of the strain. There is a
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
available which reduces the severity and incidence of disease. Some countries in Europe have successfully eradicated the disease by applying a strict culling policy. Infection can occur in cattle of any age, but it is most commonly seen between the ages of 6 and 18 months.


Transmission

BoHV-1 enters the animal through the
mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...
in the respiratory tract or genital tracts. The main mode of disease transmission is direct nose-to-nose contact between an infected and a susceptible animal. This is made possible because of the virus sloughing off into the mucus. Aerosols have to be exhaled, sneezed, or coughed from an infected animal during viral shedding in order for transmission to occur. Transmission also originates from contaminated semen through use of live breeding or AI; bulls that have been affected genitally may shed the virus in their semen. Once infected it is hard for the animal to get rid of BoHV-1 because it has many mechanisms to evade the hosts’ immune systems involved in both
innate immunity The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune s ...
and
adaptive immunity The adaptive immune system (AIS), also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized cells, organs, and processes that eliminate pathogens specifically. The ac ...
. The virus degrades interferon regulatory factor 3 (IRF3), effectively halting transcription of
interferon type 1 The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T cell, T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p2 ...
. Interferons are a component of innate immunity involved in inhibiting
viral replication Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome ...
in a host cell, as well as activating immune cells. BoHV-1 is also able to evade adaptive immune cells by inducing
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
in
CD4+ cells In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic c ...
, which assist in activating
T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...
s when
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
s are present. This down regulates the number of immune cells that recognize the virus, allowing the virus to evade detection and elimination. The virus has many other evasion strategies against the host's immune system contributing to the virus being able to maintain lifelong infection in the animal. After primary infection of BoHV-1, the latent infection is quite often found in the
trigeminal ganglion The trigeminal ganglion (also known as: Gasserian ganglion, semilunar ganglion, or Gasser's ganglion) is the sensory ganglion of each trigeminal nerve (CN V). The trigeminal ganglion is located within the trigeminal cave (Meckel's cave), a cav ...
of the cow, although on occasion infection can enter the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
. These latent infections can possibly reactivate, with or without clinical symptoms, under conditions of stress or by experimental methods. Infected animals will be continuous shedders throughout their lifetime when the virus reactivates; therefore, successfully propagating the disease. The virus sheds in such high titers that it will spread rapidly throughout a herd. Even though cattle might not be showing clinical signs they can still spread the disease. Aside from cattle, studies experimentally infecting animals have shown that goats and buffalo can act as reservoirs for BoHV-1, as well as red deer, sheep, swine, and reindeer. Shedding begins from the nasal mucosa as soon as infection occurs, and the virus has replicated in the upper respiratory tract. During replication in the respiratory tract cells of the epithelial will undergo
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
. The necrosis in the epithelial will result in an entry site for secondary infections that may result in shipping fever.


Clinical signs


Infectious bovine rhinotracheitis

The respiratory disease caused by BoHV-1 is commonly known as infectious bovine rhinotracheitis. This disease affects the upper respiratory tract as well as the reproductive tract of cattle, and is commonly found in
feedlot A feedlot or feed yard is a type of animal feeding operation (AFO) which is used in intensive animal farming, notably beef cattle, but also swine, horses, sheep, turkeys, chickens or ducks, prior to slaughter. Large beef feedlots are called conc ...
s across North America. Clinical symptoms include
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
, serous to mucopurulent nasal discharge, coughing, sneezing, difficulty breathing,
conjunctivitis Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...
and loss of appetite. Ulcers commonly occur in the mouth and nose. Mortality may reach 10 percent. IBR can also cause
abortion Abortion is the early termination of a pregnancy by removal or expulsion of an embryo or fetus. Abortions that occur without intervention are known as miscarriages or "spontaneous abortions", and occur in roughly 30–40% of all pregnan ...
. This generally occurs in mid-gestation when a susceptible cow is infected with BoHV-1. A viraemia occurs and subsequently the virus crossed the placenta and causes organ necrosis in the fetus. BoHV-1 also causes a generalized disease in newborn calves, characterized by enteritis and death.


Infectious pustular vulvovaginitis and infectious balanoposthitis

The genital disease causes infectious pustular vulvovaginitis in cows and infectious balanoposthitis in bulls. Symptoms include
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
, depression, loss of appetite, painful urination, a swollen
vulva In mammals, the vulva (: vulvas or vulvae) comprises mostly external, visible structures of the female sex organ, genitalia leading into the interior of the female reproductive tract. For humans, it includes the mons pubis, labia majora, lab ...
with pustules, ulcers, vesicles and erosions in cows, and pain on sexual contact in bulls. In both cases lesions usually resolve within two weeks.


Diagnosis

Clinical signs and history are normally enough to make a preliminary diagnosis. To definitively diagnose the infection the virus should be identified in the tissues by virus isolation or PCR, or in bulk milk samples by
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...
.
Serology Serology is the scientific study of Serum (blood), serum and other body fluids. In practice, the term usually refers to the medical diagnosis, diagnostic identification of Antibody, antibodies in the serum. Such antibodies are typically formed in r ...
may be performed to identify latent carriers, but it is not completely reliable as not all of the infected animals have detectable antibodies.


Treatment and control

Treatment is symptomatic. Anti-inflammatories reduce fever and provide pain relief.
Antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
may be necessary if a secondary infection occurs.
Vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
is widely used both to protect cattle clinically in the case of infection and significantly reduce the shedding of the virus. Vaccination provides
herd immunity Herd immunity (also called herd effect, community immunity, population immunity, or mass immunity) is a form of indirect protection that applies only to contagious diseases. It occurs when a sufficient percentage of a population has become i ...
, which lowers the likelihood of an animal coming into contact with an infected animal. Both inactivated and live
attenuated vaccine An attenuated vaccine (or a live attenuated vaccine, LAV) is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live"). Attenuation takes an infectious agent and alters it so that it becomes harmless or le ...
s are available. Immunity usually lasts approximately six months to one year. Marker vaccines are also available and recommended. Marker vaccines, also known as DIVA (differentiation of infected from vaccinated animals), have become popular in order to distinguish vaccinated animals from infected animals. A marker vaccine uses either deletion mutants or a virion subunit, such as glycoprotein E. Studies show that vaccinating after an animal has been infected decreases shedding of the disease and reduces reactivation of the latent virus, although not completely. Using a killed gE deleted marker vaccine after infection will reduce viral excretion following reactivation, using a dexamethasone treatment. Animals showing clinical signs should be
quarantine A quarantine is a restriction on the movement of people, animals, and goods which is intended to prevent the spread of disease or pests. It is often used in connection to disease and illness, preventing the movement of those who may have bee ...
d to stop the spread of the virus. The use of quarantine in herds with BoHV-1 is not ideal control program, as it is a latent virus and results in lifelong infection. However, new animals coming to a farm, or crossing borders, should be quarantined while tests for the virus are being undergone. Quarantine will also help contain the spread after an outbreak.


Eradication

Countries such as Austria, Denmark, Finland, Sweden, Italy, Switzerland and Norway have eradicated the disease, while Canada and the United States have control programs in place for it. Eradication of the disease is a time-consuming process and requires diligent testing to be granted a disease free status. The possibilities of eradication rely upon whether the herd is vaccinated and the reactivation potential of the virus. In a small, vaccinated herd BoHV-1 can be eradicated within one or two decades, whereas in a large herds eradication is unlikely. Eradication was accomplished in Switzerland in 5 years using a four-step protocol focusing on preventions on transmission with
trade barriers Trade barriers are government-induced restrictions on international trade. According to the theory of comparative advantage, trade barriers are detrimental to the world economy and decrease overall economic efficiency. Most trade barriers work o ...
, slaughtering animals with antibodies to BHV-1, detection and eradication of further reservoirs (feedlot cattle), and then putting in place a monitoring program to maintain the control. This cost Switzerland a lot of money as they compensated producers who culled their seropositive animals. Eradication is a difficult goal for this disease, but being disease free opens barriers of trade with countries that have eradicated it as well, and saves producers money from the virus’ effects.


Economic impact

BoHV-1 is a source of economic loss in both the
dairy A dairy is a place where milk is stored and where butter, cheese, and other dairy products are made, or a place where those products are sold. It may be a room, a building, or a larger establishment. In the United States, the word may also des ...
, and the beef industries in Canada due to a decrease in production, a higher susceptibility to secondary infections, and the occurrences of abortions. A particularly great cost associated with BoHV-1 involves its contribution to causing BRD (shipping fever), which is estimated to cost $500 million to US feedlots annually. It is also found economically important due to its association with reproductive problems, as study in Ethiopia depicted (Begna, 2021):The prevalence of IBR/BoHV-1 antibodies based on the history of reproductive disorders were varies among those have the history and the counterparts. Analysis of data revealed significantly higher seroprevalence of IBR/BoHV-1 antibodies in animal with history of repeat breeding (45.76%), retained fetal membrane (42.5%) and stillbirth (60.86%), than animals without the problems.


See also

* Bovine herpesvirus (disambiguation)


References


Further reading

* {{DEFAULTSORT:Bovine Herpesvirus 1 Herpes 1 Varicelloviruses Animal viral diseases Pneumonia Animal vaccines