Bovine herpesvirus 1 - AbsoluteAstronomy.com

Introduction

Bovine herpesvirus 1 (BHV-1) is a virus of the family Herpesviridae
Herpesviridae
The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses...

and the subfamily Alphaherpesviridae, known to cause several diseases worldwide in cattle

Cattle

Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...

, including rhinotracheitis, vaginitis
Vaginitis
Vaginitis is an inflammation of the vagina. It can result in discharge, itching and pain, and is often associated with an irritation or infection of the vulva. It is usually due to infection. The three main kinds of vaginitis are bacterial vaginosis , vaginal candidiasis, and trichomoniasis. A...

, balanoposthitis
Balanoposthitis
-Background:Balenoposthitis is defined as the inflammation of the foreskin and glans in uncircumcised males. Balanoposthitis occurs over a wide age range and may have any of multiple bacterial or fungal origins or be caused by contact dermatitis...

, abortion
Abortion
Abortion is defined as the termination of pregnancy by the removal or expulsion from the uterus of a fetus or embryo prior to viability. An abortion can occur spontaneously, in which case it is usually called a miscarriage, or it can be purposely induced...

, conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...

, and enteritis
Enteritis
In medicine, enteritis, from Greek words enteron and suffix -itis , refers to inflammation of the small intestine. It is most commonly caused by the ingestion of substances contaminated with pathogenic microorganisms. Symptoms include abdominal pain, cramping, diarrhea, dehydration and fever...

. BHV-1 is also a contributing factor in shipping fever, also known as Bovine Respiratory Disease (BRD). It is spread horizontally
Horizontal transmission
Horizontal transmission is the transmission of a bacterial, fungal, or viral infection between members of the same species that are not in a parent-child relationship....

through sexual contact, artificial insemination

Artificial insemination

Artificial insemination, or AI, is the process by which sperm is placed into the reproductive tract of a female for the purpose of impregnating the female by using means other than sexual intercourse or natural insemination...

, and aerosol transmission and it may also be transmitted vertically
Vertical transmission
Vertical transmission, also known as mother-to-child transmission, is the transmission of an infection or other disease from mother to child immediately before and after birth during the perinatal period. A pathogen's transmissibility refers to its capacity for vertical transmission...

across the placenta. BHV-1 can cause both clinical and subclinical infections, depending on the virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

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, BHV-1 causes a lifelong latent infection and sporadic shedding of the virus. The sciatic nerve

Sciatic nerve

The sciatic nerve is a large nerve fiber in humans and other animals. It begins in the lower back and runs through the buttock and down the lower limb...

and trigeminal nerve

Trigeminal nerve

The trigeminal nerve contains both sensory and motor fibres. It is responsible for sensation in the face and certain motor functions such as biting, chewing, and swallowing. Sensory information from the face and body is processed by parallel pathways in the central nervous system...

are the sites of latency

Virus latency

Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection...

. A reactivated latent carrier is normally the source of infection in a herd. The clinical signs displayed are dependent on the virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

of the strain. There is a vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

available which reduces the severity and incidence of disease. Some countries in Europe have successfully eradicated
Eradication of infectious diseases
Eradication is the reduction of an infectious disease's prevalence in the global host population to zero. It is sometimes confused with elimination, which describes either the reduction of an infectious disease's prevalence in a regional population to zero, or the reduction of the global prevalence...

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

BHV-1 enters the animal through the mucous membrane
Mucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...

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
Artificial insemination
Artificial insemination, or AI, is the process by which sperm is placed into the reproductive tract of a female for the purpose of impregnating the female by using means other than sexual intercourse or natural insemination...

; 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 BHV-1 because it has many mechanisms to evade the hosts’ immune systems involved in both innate immunity and adaptive immunity
Adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...

. The virus degrades interferon regulatory factor 3
IRF3
Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.- Function :IRF3 is a member of the interferon regulatory transcription factor family. IRF3 was originally discovered as a homolog of IRF1 and IRF2...

(IRF3), effectively halting transcription of interferon type 1
Interferon type I
Human type I interferons comprise a vast and growing group of IFN proteins.All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor that consists of IFNAR1 and IFNAR2 chains....

. Interferons are a component of innate immunity involved in inhibiting viral replication
Viral replication
Viral replication is the term used by virologists to describe 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. From the perspective of the virus, the purpose of viral replication is...

in a host cell, as well as activating immune cells. BHV-1 is also able to evade the adaptive immune cells
Adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...

by inducing apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

in CD4+ cells
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

, which assist in activating T cells
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

when antigens
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

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 BHV-1, the latent infection
Virus latency
Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection...

is quite often found in the trigeminal ganglion
Trigeminal ganglion
The trigeminal ganglion is a sensory ganglion of the trigeminal nerve that occupies a cavity in the dura mater, covering the trigeminal impression near the apex of the petrous part of the temporal bone.-Relations:It is somewhat crescentic in shape, with its convexity...

of the cow, although on occasion infection can enter the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

. These latent infections
Virus latency
Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection...

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 BHV-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
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

. The necrosis in the epithelial will result in an entry site for secondary infections that may result in Shipping Fever.

Infectious Bovine Rhinotracheitis

The respiratory disease caused by BHV-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 feedlots
Feedlot
A feedlot or feedyard is a type of animal feeding operation which is used in factory farming for finishing livestock, notably beef cattle, but also swine, horses, sheep, turkeys, chickens or ducks, prior to slaughter. Large beef feedlots are called Concentrated Animal Feeding Operations . They...

across North America .

Clinical symptoms include fever, serous to mucopurulent nasal discharge, coughing, sneezing, difficulty breathing, conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...

and loss of appetite. Ulcers commonly occur in the mouth and nose. Mortality may reach 10 percent.

IBR can also cause abortion
Abortion
Abortion is defined as the termination of pregnancy by the removal or expulsion from the uterus of a fetus or embryo prior to viability. An abortion can occur spontaneously, in which case it is usually called a miscarriage, or it can be purposely induced...

. This generally occurs in mid-gestation when a susceptible cow is infected with BHV-1. A viraemia occurs and subsequently the virus crossed the placenta and causes organ necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

in the fetus. BHV-1 also causes a generalized disease in newborn calves, characterized by enteritis and death.

Infectious Pustular Vulvovaginitis & Infectious Balanoposthitis

The genital disease causes infectious pustular vulvovaginitis in cows and infectious balanoposthitis in bulls. Symptoms include fever, depression, loss of appetite, painful urination, a swollen vulva
Vulva
The vulva consists of the external genital organs of the female mammal. This article deals with the vulva of the human being, although the structures are similar for other mammals....

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
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

.

Serology
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...

may be performed to identify latent carriers, but its is not completely reliable as not all of the infected animals have detectable antibodies.

Treatment & Control

Treatment is symptomatic. Anti-inflammatories

Anti-inflammatory

Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....

reduce fever and provide pain relief. Antibiotics may be necessary if a secondary infection occurs.

Vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...

is widely use both protect cattle clinically in the case of infection and significantly reduce the shedding of the virus. Vaccination provides herd immunity
Herd immunity
Herd immunity describes a form of immunity that occurs when the vaccination of a significant portion of a population provides a measure of protection for individuals who have not developed immunity...

, which lowers the likelihood of an animal coming into contact with an infected animal. Both inactivated and live attenuated vaccines 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 quarantined

Quarantine

Quarantine is compulsory isolation, typically to contain the spread of something considered dangerous, often but not always disease. The word comes from the Italian quarantena, meaning forty-day period....

to stop the spread of the virus. The use of quarantine in herds with BHV-1 is not ideal control program, as it is a latent virus and results in life long 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
Eradication of infectious diseases
Eradication is the reduction of an infectious disease's prevalence in the global host population to zero. It is sometimes confused with elimination, which describes either the reduction of an infectious disease's prevalence in a regional population to zero, or the reduction of the global prevalence...

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 BHV-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 barrier

Trade barriers are government-induced restrictions on international trade. The barriers can take many forms, including the following:* Tariffs* Non-tariff barriers to trade** Import licenses** Export licenses** Import quotas** Subsidies...

, 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

BHV-1 is a source of economic loss in both the dairy

Dairy farming

Dairy farming is a class of agricultural, or an animal husbandry, enterprise, for long-term production of milk, usually from dairy cows but also from goats and sheep, which may be either processed on-site or transported to a dairy factory for processing and eventual retail sale.Most dairy farms...

, 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 BHV-1 involves its contribution to causing BRD (Shipping Fever), which is estimated to cost $500 million dollars to US feedlots annually.