bovine herpesvirus 1 infections

International Common Names

• English: encephalitic bovine herpesvirus type 5 or type 1 infection in cattle; ibr, infectious bovine rhinotracheitis-contaminated semen; infectious bovine rhinotracheitis; infectious bovine rhinotracheitis virus, ibr, in swine; infectious bovine rhinotracheitis/infectious pustular vulvovaginitis; infectious pustular vulvovaginitis; neonatal septicemic infectious bovine rhinotracheitis, ibr

English acronym

• BHV
• IBR
• IPB
• IPV

Infectious bovine rhinotracheitis (IBR) is a contagious viral disease of cattle caused by bovine herpesvirus 1 (BHV-1) (Gibbs and Rweyemamu, 1977; Pastoret et al., 1982; Wyler et al., 1989; Tikoo et al., 1995). This virus is also responsible for infectious pustular vulvovaginitis (IPV), balanoposthitis and abortion.

IPV was the only known infection caused by BHV-1 prior to the 1950s, when the respiratory disease IBR, emerged in North America as a consequence of the intensification of cattle husbandry. The respiratory disease spread all over the world and arrived in Europe during the 1970s. The IBR form is the most frequently diagnosed BHV-1 disease.

Pathogenicity of BHV-1 can vary from mild to severe and the relative importance of each syndrome varies between countries. Although mortality is low, BHV-1 infection is economically important as it may cause a drop in production and affect trade restrictions. When animals survive, a life-long latent infection is established in sensory ganglia. Several reactivation stimuli can lead to viral re-excretion, which is responsible for the maintenance of BHV-1 within a cattle herd (Muylkens et al. 2007). The latency and reactivation cycle have a significant impact on the epidemiology and control of BHV-1. Europe has a long history of fighting against BHV-1 infections, but only a small number of countries have achieved IBR-eradication (Ackermann et al., 1990; Ackermann and Engels, 2006).

This disease is on the list of diseases notifiable to the World Organisation for Animal Health (OIE). The distribution section contains data from OIE's WAHID database on disease occurrence. Please see the AHPC library for further information on this disease from OIE, including the International Animal Health Code and the Manual of Standards for Diagnostic Tests and Vaccines. Also see the website: www.oie.int.

Subclinical infection

Infectious bovine rhinotracheitis (IBR) is a sporadic viral disease. Outbreaks are observed during winter, but the incidence of the disease is low, whatever the prevalence rate in a given region. High seroprevalence without a high incidence of disease is generally explained by the circulation of hypovirulent strains, as suggested by the results of experimental inoculation of calves with strains of varying virulence (Kaashoek et al., 1996). However, subclinical infection with a BHV-1 strain normally associated with clinically severe respiratory disease has been reported in a high health status dairy herd, which had previously been seronegative for 13 years. Although over 70% of the herd had seroconverted to BHV no clinical signs were observed apart from a slight bilateral serous ocular discharge in a few cows; performance and productivity were unaffected (Pritchard et al., 2003).

Infectious bovine rhinotracheitis (IBR)

The respiratory form is the most frequently observed disease provoked by BHV-1. It affects all categories of animals. Calves are usually protected by colostral antibodies until 3-4 months of age. The severity of clinical signs varies considerably. Because of its ability to induce immune suppression, BHV-1 is an important agent in the multifactorial disorder, bovine respiratory disease complex (Jones and Chowdhury, 2010). The virus is also responsible for a typical respiratory disease called infectious bovine rhinotracheitis (IBR).

The virus is excreted in the nasal secretions as early as 24 hours after infection. After an incubation period of 2 to 4 days, nasal secretions are more profuse and evolve from sero-mucous to mucopurulent discharge. Young animals show ptyalism. Around 4 days after the beginning of excretion, elevated temperatures are recorded, and animals are depressed and anorexic. In lactating cows, the milk production suddenly drops.

Ulcers and redness are visible on the nasal mucosa, in the pharynx and trachea (see pictures). Lesions are usually restricted in the upper respiratory tract. Bronchitis and pneumonia can also be observed, but usually as a consequence of secondary bacterial infections. Coughing and sneezing are observed. Conjunctivitis is associated with the respiratory form and is manifest by increased eye secretions.

Animals recover within 14 days, due to the rise of the specific immune response. Some highly virulent BHV-1 strains induce a high mortality rate.

Lesions are almost exclusively restricted to the upper respiratory tract: rhinitis, laryngitis and tracheitis. Respiratory mucosae are red and oedematous, foci of ulcers are observed and some lesions are haemorrhagic (Gibbs and Rweyemamu, 1977; Wyler et al., 1989; Straub, 1990).

Abortion

A review by Graham (2013) highlights the negative reproductive outcomes associated with BHV-1. Infection at the time of service may reduce fertility, with the potential to cause chronic necrotising endometritis and oophoritis, accompanied by a shortened oestrous cycle. Infection later in the oestrous cycle may result in a decreased conception rate, whereas infection later in pregnancy can lead to abortion.

Abortion is observed between 4 and 8 months of gestation. Early embryonic death can also occur. Abortion is a consequence of respiratory infection of pregnant cows. Viraemia allows the virus to enter the uterine artery and cross the placenta. Abortion is due to a lytic infection of the fetus. All internal organs of the fetus, especially the liver and renal cortex, show foci of necrosis. A generalized multifocal necrosis is diagnosed (Smith, 1997).

Infection of cows during the last trimester of gestation can lead to neonatal death, and death of weak calves can occur during the first 2 weeks of life (Thiry et al., 1984).

Infectious pustular vulvovaginitis (IPV) - infectious pustular balanoposthitis (IPB)

A pustular inflammation occurs in the male or female genital mucosa, together with a rise in body temperature: up to 41.5°C. The genital mucosa is red and oedematous, and vesicles and pustules evolve into ulcers. The lesions resolve within 1 to 2 weeks (Straub, 1990).

Metritis

Metroperitonitis has been observed in cows infected with BHV-1 around parturition, and especially after caesarean section (Lomba et al., 1976).

Encephalitis

Encephalitis cases have been mostly reported in calves but can also occur in older animals (Roels et al., 2000). In the case of bovine encephalitis, the distinction must be made between BHV-1 and BHV-5, the latter being the usual etiological agent of bovine encephalitis (Meyer et al., 2001).

Neonatal diseases

Neonatal calves often succumb after a generalized infection. They show coughing, nasal and ocular discharge, bronchopneumonia, diarrhoea, ulcers in the digestive tract and hyperthermia. The lesions can be concentrated in the mouth, with ulcers and profuse salivation. A pure respiratory form is rarely observed in neonates. Encephalitis has been observed in 3 to 8 day-old calves (Thiry et al., 1984).

Other clinical signs

Although BHV-1 has been associated with clinical mastitis, there is little concrete evidence for its involvement in the syndrome (Gourlay et al., 1974). Isolation of BHV-1 from milk can be simply a consequence of viraemia. BHV-1 has also been isolated from ulcerative lesions of the mouth and the interdigital space (Dhennin et al., 1979), thus potentially leading to confusion with other vesicular diseases such as foot and mouth disease, vesicular stomatitis and mucosal disease (Holliman, 2005).

BHV-1 is excreted in the respiratory, ocular and genital secretions of infected cattle. Nasal secretions contain high concentrations of virus and constitute the main source of infection. The virus is transmitted by direct contact, by aerosol over short distances, or by material or clothes contaminated by infectious mucus. Sperm can be infected and the virus can be transmitted genitally. As the virus is well preserved in liquid nitrogen, artificial insemination must only be made with sperm from BHV-1 free bulls. Embryo transfer is also a potential risk for BHV-1 transmission. Embryo treatment with trypsin removes the virus, which may have been adsorbed onto the pellucid membrane.

After virus replication at the portal of entry (nasal or genital mucosa),BHV-1 disseminates in the blood, the nerves and by cell-to-cell transmission inside the infected tissue. Primary infection is followed by a transient viraemia, allowing the virus to infect secondary sites such as the digestive tract, udder, fetus and ovaries (Miller et al., 1985). Infection of the neonate provokes a generalized fatal infection in the absence of specific colostral antibodies. In other animals, the infection of peripheral nerves at the site of infection induces a retrograde axonal transport of the virus to the regional nervous ganglia, i.e. the trigeminal ganglion in the case of respiratory infection and the sacral ganglion after genital infection. Other sites of latency cannot be excluded, such as the tonsils (Winkler et al., 2000).

After respiratory infection, virus is excreted in the nasal secretions at very high titres - up to 10¹⁰ tissue culture infectious doses (TCID₅₀) - over 10 to 16 days. Virus replication is controlled by non-specific, followed by specific, immune responses (Denis et al., 1994). The virus establishes a latent infection after primary infection, re-infection or vaccination with an attenuated virus. Latent infection is lifelong and may be interrupted by virus reactivation and re-excretion. BHV-1 reactivation is provoked by several stimuli. These are transport, parturition, glucocorticoid treatment, viral superinfection and infestation with Dictyocaulus viviparus (Thiry et al., 1986). Re-excretion is usually clinically silent, but the amount of re-excreted virus can be high and the process lasts for several days. The level of re-excretion is directly related to the level of the specific immune response at the time of reactivation (Engels and Ackermann, 1996; Pastoret et al., 1984; Lemaire et al., 1994; Thiry et al., 1986, 1999).

Recombination is an important source of genetic variation in BHV-1, like other herpesviruses, and may be significant when vaccines containing deletion mutants are used. Recombination of two BHV-1 mutants lacking either glycoprotein C (gC-) or E (-gE-) was found to be a frequent event in calves coinfected with these strains. After reactivation from latency, no viruses of the originally inoculated mutants were detected, although gC+/gE- mutants, when inoculated alone, were detected after reactivation treatment (Schynts et al., 2003).

Transmission

BHV-1 is transmitted by nasal or genital secretions. Transmission is mainly direct, from animal to animal, by the respiratory or the genital route. Indirect transmission via infected clothes or materials is also possible (Wentink et al., 1993). Aerosols can disseminate the virus over 4 meters in field conditions (Mars et al., 2000). Vertical transmission occurs in cows, when the virus crosses the placenta and infects the fetus.

Morbidity and mortality

The clinical consequences of BHV-1 circulation in a herd depend on the virulence of the prevalent strain. Where virulent strains circulate, morbidity rate is up to 100% in a naïve herd. Otherwise morbidity rate is approximately 20%. The mortality rate varies between 0 and 10%. Genital strains causing IPV are less virulent (Straub, 1990).

Temporal and spatial evolution

In a herd, BHV-1 circulation is initiated by virus reactivation and re-excretion in a latently infected animal already present, or more often by the introduction of an acutely or latently infected animal. In the absence of clinical signs, virus circulation is evidenced by seroconversion in young animals (van Nieuwstadt and Verhoeff, 1983). Two patterns of virus circulation are observed: rapid seroconversion of seronegative animals, most likely due to a virulent strain; or seroconversion of animals over a long period of time (several weeks to several months) usually due to hypovirulent strains (Van Nieuwstadt and Verhoeff, 1983). The basic reproduction ratio (R₀) was calculated in a herd after experimental reactivation of virus in three seropositive cows. All seronegative animals seroconverted over a period of 4 weeks and an average of 7 new cases were generated by each infected animal (Hage et al., 1996). This result shows the rapid transmission of the virus in a susceptible herd.

A study of natural transmission of BHV-1 in the Netherlands involved 50 herds with 3300 head of cattle. Herds were divided into 3 groups: seronegative, vaccinated, and mixed. Three outbreaks of BHV1 occurred due to the introduction of infectious cattle, and another due to reactivation of latent BHV1 in seropositive cattle. The basic reproduction ratio within herds was estimated to be at least 4. Only one of the outbreaks led to secondary outbreaks in seronegative herds; the between herds basic reproduction ratio was estimated to be 0.6 (Hage et al., 2003).

Between herds transmission is a major risk of BHV-1 circulation. However, it can be better controlled than within herd spread. Sanitary measures can be taken to prevent the introduction of seropositive animals or animals originating from a seropositive herd. Airborne transmission of BHV-1 has been demonstrated over short distances and can provide an explanation of between herds transmission, without the introduction of any new animal (Mars et al., 1999).

Risk factors

The risk factors for BHV-1 infection in a herd have been studied on dairy farms. BHV-1 positive farms purchase cattle and participate in cattle shows more often than negative farms. Positive farms have also had more visitors who are less likely to use dedicated farm clothing. Positive farms are also situated closer to other cattle farms (van Schaik et al., 1998). As cattle are the main source of virus spread, risk factors for virus infection are associated with cattle movement (Wentink et al., 1993).

The economic importance of BHV-1 infection can be envisaged from two points of view:

1. At the herd level: an IBR outbreak can cause a severe epidemic of respiratory disease with direct economic losses due to death, growth retardation, decreased milk production and abortion (Hage et al., 1998). The genital IPV form is usually much less severe.


2. At a regional level: the status ‘BHV-1 free’ can confer commercial advantages to a country or a region. European member states such as Denmark, Finland, Sweden and Austria are officially free of BHV-1. Only cattle, sperm and embryos from BHV-1 free herds or countries may be imported into these countries.

The impact of the infection is directly linked to the prevalence of seropositive animals. This value can vary from 0% in countries free of the disease, like Denmark and Sweden, to 67% in Belgium (Boelaert et al., 2000) and 84 % in the Netherlands (van Wuyckhuise et al., 1998). However, exact figures that describe actual losses have not been calculated.

No antiviral drugs are used. Antimicrobial therapy is needed to overcome bacterial superinfection. The use of corticosteroids is contraindicated since these drugs provoke BHV-1 reactivation and are likely to aggravate the severity of the outbreak by increasing virus circulation. Therefore, only nonsteroidal anti-inflammatory compounds, such as carprofen, are recommended for use (Eltok and Eltok, 2004). Immunomodulators have been found to limit the spread of infection, decrease viral shedding and reduce the severity of clinical signs in experimental BHV-1 infection in calves (Castrucci et al., 2000).