Bovine Herpesvirus 1
Bovine herpesvirus 1 (BHV-1) infections are widespread in the cattle population.
In feedlot cattle, the respiratory form of BHV-1 is most common. The viral infection alone is not life-threatening but predisposes cattle to secondary bacterial pneumonia, which can result in death.
In breeding cattle, abortion or genital infections are more common. Genital infections can occur in bulls (infectious pustular balanoposthitis) and cows (infectious pustular vulvovaginitis) within 1–3 days of mating or close contact with an animal infected with BHV-1. Transmission can occur in the absence of visible lesions and via artificial insemination with semen from subclinically infected bulls.
Cattle with latent BHV-1 infections generally show no clinical signs when the virus is reactivated; however, they serve as a source of infection for other susceptible animals. This disease can be effectively controlled with modified live virus vaccination.
Etiology and Epidemiology
BHV-1 is associated with the following clinical signs in cattle:
infectious bovine rhinotracheitis (IBR)
infectious pustular vulvovaginitis
balanoposthitis
conjunctivitis
abortion
encephalomyelitis
mastitis
Only a single serotype of BHV-1 is recognized; however, 3 subtypes of BHV-1 have been described on the basis of endonuclease cleavage patterns of viral DNA:
BHV-1.1 (respiratory subtype)
BHV-1.2 (genital subtype)
BHV-1.3 (encephalitic subtype)
BHV-1.3 has been reclassified as a distinct herpesvirus designated BHV-5.
Clinical Findings
The incubation period for the respiratory and genital forms of BHV-1 is 2–6 days. In the respiratory form, clinical signs range from mild to severe, depending on the presence of secondary bacterial pneumonia. Clinical signs include high fever, anorexia, coughing, excessive salivation, nasal discharge that progresses from serous to mucopurulent, conjunctivitis with lacrimal discharge, inflamed nares (hence the common name “red nose”), and dyspnea if the larynx becomes occluded with purulent material.
Nasal lesions consist of numerous clusters of grayish necrotic foci on the mucous membrane of the nasal septum, just visible inside the external nares. They may later be accompanied by pseudodiphtheritic yellowish plaques. Conjunctivitis with corneal opacity may occur as the only clinical sign of BHV-1 infection (see IBR with conjunctivitis image). In the absence of bacterial pneumonia, recovery generally occurs 4–5 days after the onset of clinical signs.
Courtesy of Dr. John Campbell.
Abortions may occur concurrently with respiratory disease or may occur up to 100 days after infection. They can occur regardless of disease severity in the dam. Abortions generally occur during the second half of pregnancy; however, early embryonic death is possible.
With genital infections, the first clinical signs are frequent urination, elevation of the tailhead, and mild vaginal discharge (see vulvitis and vaginitis). The vulva is swollen, and small papules, followed by erosions and ulcers, are present on the mucosal surface. If secondary bacterial infections do not occur, animals recover in 10–14 days. With bacterial infection, uterine inflammation and transient infertility may occur, with purulent vaginal discharge for several weeks. In bulls, similar lesions occur on the penis and prepuce.
BHV-1 infection can be severe in young calves and cause generalized disease. Pyrexia, ocular and nasal discharges, respiratory distress, diarrhea, incoordination, and eventually convulsions and death can occur in a short period after generalized viral infection.
Gross and Histopathological Findings
In uncomplicated IBR infections, most lesions are restricted to the upper respiratory tract and trachea. Petechial to ecchymotic hemorrhages may occur in the mucous membranes of the nasal cavity and paranasal sinuses. Foci of necrosis develop in the nose, pharynx, larynx, and trachea. Lesions may coalesce to form plaques.
The sinuses are often filled with serous or serofibrinous exudate. As the disease progresses, the pharynx becomes covered with serofibrinous exudate, and blood-tinged fluid may be present in the trachea. Pharyngeal and pulmonary lymph nodes may be acutely swollen and hemorrhagic. Tracheitis may extend into the bronchi and bronchioles; when this occurs, epithelium is sloughed in the airways. Viral lesions are often masked by secondary bacterial infections.
In young animals with generalized BHV-1 infection, erosions and ulcers overlaid with debris can occur in the nose, esophagus, and forestomachs. In addition, white foci can occur in the liver, kidney, spleen, and lymph nodes. Aborted fetuses may have pale, focal, necrotic lesions in all tissues but especially in the liver.
Diagnosis
Characteristic lesions
Viral isolation
Paired serological testing
PCR assay, immunohistochemical testing, or antibody staining
Uncomplicated BHV-1 infections can be diagnosed based on characteristic clinical signs and lesions of rhinitis, tracheitis, and conjunctivitis. However, because the severity of disease can vary, BHV-1 should be differentiated from other viral infections by viral isolation. Samples should be taken early in the disease, and a diagnosis should be possible in a few days, when viral isolation results are received from the diagnostic laboratory. A rise in serum antibody titer also can be used to confirm a diagnosis.
It is not possible to detect a rising antibody titer in abortions, because infection generally occurs a considerable length of time before the abortion and titers are already maximal. BHV-1 abortion can be diagnosed by identifying characteristic lesions and demonstrating the virus in fetal tissues by PCR assay, virus isolation, and immunoperoxidase or fluorescent antibody staining.
If the dam dies, gross and microscopic lesions detected shortly after death can help to establish a diagnosis. PCR assay can be used to identify antigen in a variety of tissues or exudates.
Treatment and Control
Antimicrobial treatment of secondary bacterial infection
Modified live or inactivated virus vaccines
Biosecurity
Eradication programs
Antimicrobial treatment is indicated to prevent or treat secondary bacterial pneumonia in patients with BHV-1. General recommendations for control are as discussed under bovine respiratory disease. Immunization with modified live or killed virus vaccines generally provides adequate protection against clinical signs of disease. Both parenteral and intranasal modified live virus vaccines are available; however, parenteral vaccines may cause abortion in naive pregnant cattle. Intranasal modified live virus vaccines can be used safely in all pregnant cattle.
Modified live virus vaccines provide a longer duration of immunity and often are the vaccines of choice in feedlots where potential exposure to BHV-1 is high. Breeding and replacement heifers and bulls should be immunized at 6–8 months old, before breeding, and yearly thereafter. Feeder calves should be immunized 2–3 weeks before entry into the feedlot. Many feedlot veterinarians recommend a second vaccination when animals arrive to provide good duration of immunity.
A number of western European countries have eradicated or are attempting to eradicate BHV-1 from their domestic cattle populations. Eradication of the virus is possible by a combination of serological surveillance, culling of reactors, biosecurity, and vaccination. To aid in eradication, deletion mutant vaccines have been developed that permit discrimination between antibody produced in response to the vaccine and antibody produced in response to natural exposure.
Key Points
Bovine herpesvirus (BHV-1) can cause rhinotracheitis, pustular vulvovaginitis, balanoposthitis, conjunctivitis, and abortion in cattle.
BHV-1 causes systemic, highly fatal disease in newborn calves.
Latent carrier animals are often the source of infection.
Lesions include erosions and fibrinous plaques in nasal passages and the trachea.
BHV-1 can be controlled effectively with modified live virus vaccines.
For More Information
Infectious bovine rhinotracheitis/infectious pustular vulvovaginitis. World Organisation for Animal Health.
IBR (infectious bovine rhinotracheitis). National Animal Disease Information Service.
Bovine Respiratory Syncytial Virus
Bovine respiratory syncytial virus (BRSV) infections associated with respiratory disease occur predominantly in young beef and dairy cattle less than 6 months old; however, adult cattle can also be affected. BRSV can be considered a primary bovine respiratory disease (BRD) pathogen and is also a component of the BRD complex. Passively derived immunity does not appear to prevent BRSV infections but decreases severity of disease. Initial exposures to the virus are associated with severe respiratory disease; subsequent exposures result in mild to subclinical disease.
BRSV is an important virus in the BRD complex because of its frequency of occurrence, predilection for the lower respiratory tract, and ability to predispose the respiratory tract to secondary bacterial infection. In outbreaks, morbidity rates tend to be high, and the case fatality rate can be 0–20%.
Etiology
BRSV is an RNA virus classified as a pneumovirus in the Paramyxovirus family. BRSV was named for its characteristic cytopathic effect: the formation of syncytial cells. In addition to cattle, sheep and goats can be infected by respiratory syncytial viruses. Human respiratory syncytial virus (RSV) is an important respiratory pathogen in infants and young children. Antigenic subtypes are known to exist for human RSV, and preliminary evidence suggests antigenic subtypes of BRSV may exist.
BRSV is distributed worldwide and is ubiquitous in the cattle population.
Clinical Findings and Lesions
Common clinical signs in BRSV include the following:
fever (40–42ºC [104–108ºF)
listlessness
decreased feed intake
increased respiratory rate
cough
nasal and lacrimal discharge
Dyspnea, possibly with open-mouthed breathing, can become pronounced in the later stages of BRSV. Subcutaneous emphysema may occur secondary to the tracking of air from ruptured bullae along fascial planes. Secondary bacterial pneumonia is a frequent occurrence. A small percentage of cases may develop fatal interstitial pneumonia.
Courtesy of Dr. John Campbell.
Gross lesions include a diffuse interstitial pneumonia with subpleural and interstitial emphysema along with interstitial edema (see BRSV with pathological lesions image). These lesions are similar to, and must be differentiated from, other causes of interstitial pneumonia. Bacterial bronchopneumonia is usually present. Histological examination reveals syncytial cells in bronchiolar epithelium and lung parenchyma, intracytoplasmic inclusion bodies, proliferation and/or degeneration of bronchiolar epithelium, alveolar epithelialization, edema, and hyaline membrane formation.
Diagnosis
PCR assay or immunohistochemical testing
Paired serological testing
Diagnosis of BRSV requires laboratory confirmation through postmortem samples or through nasopharyngeal swabs or transtracheal aspirates. BRSV is a difficult pathogen to isolate, although chances of isolation may improve when sampling animals in the incubation or acute phases of infection. Although virus isolation is difficult, PCR assay is a useful and rapid method commonly used to detect viral antigen. Other procedures that have proved useful in detection of BRSV antigen are fluorescent antibody and immunoperoxidase staining.
Paired acute and convalescent serum samples can be used to establish a diagnosis. However, the antibody titer of animals with well-developed clinical signs of disease may be higher in the acute sample than in the sample taken 2–3 weeks later because the antibody response often develops rapidly, and clinical signs follow virus infection by up to 7–10 days. Single serum samples with high antibody titers from a number of animals in a respiratory outbreak can help diagnosis if coupled with clinical signs. However, calves that become infected with BRSV in the presence of passively derived antibody may not seroconvert.
Treatment and Prevention
Antimicrobials
Supportive treatment
Treatment of BRSV focuses on using antimicrobials to control secondary bacterial pneumonia. No specific treatment exists for viral interstitial pneumonia. Supportive treatment and correction of dehydration may be necessary. Animals can recover in several days without treatment. (General principles of control are discussed in the topic Enzootic Pneumonia of Calves.)
Killed and modified live virus vaccines are available in injectable and intranasal formats. Although vaccination may decrease losses associated with BRSV, few field trials exist to evaluate the efficacy of these vaccines. Some recent studies suggest that the use of intranasal modified live virus vaccines against respiratory viruses may alter the microbial community and balance of opportunistic pathogens in the respiratory tract of cattle (1, 2). However, the implications of these changes in disease susceptibility are still unclear.
Key Points
BRSV occurs predominantly in young cattle or calves less than 6 months old; however, adult cattle can be affected.
BRSV can be part of the respiratory disease complex or can cause viral pneumonia as primary infection.
Diagnosis is difficult but may be confirmed by PCR assay or serological testing.
Vaccines are available, but studies regarding their real-world effectiveness as they are used in commercial settings are lacking.
For More Information
Makoschey B, Berge AC. Review on bovine respiratory syncytial virus and bovine parainfluenza – usual suspects in bovine respiratory disease – a narrative review. BMC Vet Res. 2021;17(261).
References
Powledge SA, McAtee TB, Woolums AR, et al. Clinical and microbiological effects in high-risk beef calves administered intranasal or parenteral modified-live virus vaccines. J Anim Sci. 2022;100(11):skac249. doi:10.1093/jas/skac249
McAtee TB, Pinnell LJ, Powledge SA, Wolfe CA, Morley PS, Richeson JT. Effects of respiratory virus vaccination and bovine respiratory disease on the respiratory microbiome of feedlot cattle. Front Microbiol. 2023;14:1203498. doi:10.3389/fmicb.2023.1203498
Parainfluenza-3 Virus in Cattle
Parainfluenza-3 virus (PI-3) is an RNA virus classified in the Paramyxovirus family. Infections due to PI-3 are common in cattle. Although PI-3 is capable of causing disease, it is considered a minor pathogen and usually associated with mild to subclinical infections. PI-3's most important role is serving as an initiator that can lead to development of secondary bacterial pneumonia.
Clinical signs of PI-3 virus include pyrexia, cough, serous nasal and lacrimal discharge, increased respiratory rate, and increased breath sounds. The severity of clinical signs increases with the onset of bacterial pneumonia.
Lesions include cranioventral lung consolidation, bronchiolitis, and alveolitis with marked congestion and hemorrhage. Inclusion bodies may be identified.
Fatalities from uncomplicated PI-3 pneumonia are rare; most fatal cases have concurrent bacterial bronchopneumonia.
Diagnostic procedures for PI-3 are similar to those for bovine respiratory syncytial virus.
Treatment of PI-3 virus focuses on antimicrobial treatment directed toward bacterial pneumonia. NSAIDs are also a therapeutic consideration.
Bovine Viral Diarrhea Virus
Bovine viral diarrhea virus (BVDV) is an RNA virus classified as a pestivirus in the family Flaviviridae. The role of BVDV in bovine respiratory disease as a primary pathogen has been controversial; however, the virus appears to be capable of inducing immunosuppression, allowing the development of secondary bacterial or viral pneumonia. Treatment for acute BVDV infection is supportive and includes antimicrobials to prevent or treat bacterial pneumonia.
Seroconversion to BVDV after arriving in the feedlot has been reported to be associated with the occurrence of respiratory disease in feedlot calves. Calves that arrive at the feedlot with high titers to BVDV have also been shown to be less likely to develop respiratory disease, and BVDV has been reported to be the virus most frequently associated with multiple viral respiratory infections in calves.
Killed and modified live BVD virus vaccines, including vaccines containing both the type I and type II genotypes, are available for IM administration. Vaccinating cows with modified live virus vaccines before breeding is an important strategy to prevent persistently infected calves. Testing calves for persistent infection and removing them from the pen has been used as a strategy to decrease the risk of disease within feedlots in high-risk groups. (General principles of control are discussed in the topic Enzootic Pneumonia of Calves.)
Other Bovine Respiratory Viruses
Several other viruses may potentially be involved in BRD. Bovine herpesvirus 4 has been implicated in several diseases, including BRD. Bovine adenovirus has been associated with a wide spectrum of diseases, with bovine adenovirus type 3 being the serotype most often associated with BRD. Two serotypes of bovine rhinovirus have been recognized to cause respiratory tract infections in cattle.
Other viruses reported to be associated with BRD include bovine reovirus, enterovirus, influenza type D virus, and coronavirus. Evidence is growing that bovine coronavirus may have a more important role in BRD than has been previously recognized. Bovine coronavirus may play a role in some outbreaks of calf pneumonia on pasture in beef cow-calf operations.
These bovine respiratory viruses have a role similar to that of other viruses previously discussed: ie, in combination with other stressors, they can serve as initiators of bacterial pneumonia. Vaccines are not available for prevention of these viral respiratory diseases.
