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Viral Infections Associated with Bovine Respiratory Disease Complex in Cattle


John Campbell

, DVM, DVSc, Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan

Reviewed/Revised Dec 2022 | Modified Jun 2023
Topic Resources

Bovine Herpesvirus 1

Bovine herpesvirus 1 infections are widespread in the cattle population. In feedlot cattle, the respiratory form is most common. The viral infection alone is not life-threatening but predisposes to secondary bacterial pneumonia, which may 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 infected animal. Transmission can occur in the absence of visible lesions and via artificial insemination with semen from subclinically infected bulls. Cattle with latent bovine herpesvirus 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 of Bovine Herpesvirus 1

Bovine herpesvirus 1 (BHV-1) is associated with several clinical manifestations in cattle: infectious bovine rhinotracheitis (IBR), infectious pustular vulvovaginitis, balanoposthitis, conjunctivitis, abortion, encephalomyelitis, and mastitis. Only a single serotype of BHV-1 is recognized; however, three 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), and BHV-1.3 (encephalitic subtype). BHV-1.3 has been reclassified as a distinct herpesvirus designated BHV-5.

Clinical Findings of Bovine Herpesvirus 1

The incubation period for the respiratory and genital forms of bovine herpesvirus 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 septal mucosa, just visible inside the external nares. They may later be accompanied by pseudodiphtheritic yellowish plaques. Conjunctivitis with corneal opacity may occur as the only manifestation of BHV-1 infection. In the absence of bacterial pneumonia, recovery generally occurs 4–5 days after the onset of clinical signs.

Abortions may occur concurrently with respiratory disease but may be up to 100 days after infection. They can occur regardless of the severity of disease in the dam. Abortions generally occur during the second half of pregnancy; however, early embryonic death is possible.

In genital infections, the first clinical signs are frequent urination, elevation of the tailhead, and a mild vaginal discharge. The vulva is swollen, and small papules, then 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, there may be inflammation of the uterus and transient infertility, with purulent vaginal discharge for several weeks. In bulls, similar lesions occur on the penis and prepuce. ( See also Vulvitis and Vaginitis in Large Animals Vulvitis and Vaginitis in Large Animals .)

BHV-1 infection can be severe in young calves and cause a generalized disease. Pyrexia, ocular and nasal discharges, respiratory distress, diarrhea, incoordination, and eventually convulsions and death may occur in a short period after generalized viral infection.

Gross and Histopathologic Findings

In uncomplicated IBR infections, most lesions are restricted to the upper respiratory tract and trachea. Petechial to ecchymotic hemorrhages may be found in the mucous membranes of the nasal cavity and the paranasal sinuses. Focal areas of necrosis develop in the nose, pharynx, larynx, and trachea. The lesions may coalesce to form plaques.

The sinuses are often filled with a serous or serofibrinous exudate. As the disease progresses, the pharynx becomes covered with a serofibrinous exudate, and blood-tinged fluid may be found in the trachea. The pharyngeal and pulmonary lymph nodes may be acutely swollen and hemorrhagic. The tracheitis may extend into the bronchi and bronchioles; when this occurs, epithelium is sloughed in the airways. The viral lesions are often masked by secondary bacterial infections.

In young animals with generalized bovine herpesvirus 1 infection, erosions and ulcers overlaid with debris may be found in the nose, esophagus, and forestomachs. In addition, white foci may be found in the liver, kidney, spleen, and lymph nodes. Aborted fetuses may have pale, focal, necrotic lesions in all tissues, which are especially visible in the liver.

Diagnosis of Bovine Herpesvirus 1

  • Characteristic lesions

  • Nasal swabs

  • Viral isolation

  • Paired serology

  • PCR assay, immunohistochemistry, or antibody staining

Uncomplicated bovine herpesvirus 1 infections can be diagnosed based on the characteristic clinical signs and lesions of rhinitis, tracheitis, and conjunctivitis. However, because the severity of disease can vary, it is best to differentiate BHV-1 from other viral infections by viral isolation. Samples should be taken early in the disease, and a diagnosis should be possible in 2–3 days. 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, immunoperoxidase, or fluorescent antibody staining. If the dam dies, gross and microscopic lesions detected shortly after death may help to establish a diagnosis. PCR assay can be used to identify antigen in a variety of tissues or exudates.

Treatment and Control of Bovine Herpesvirus 1

  • 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 bovine herpesvirus 1. General recommendations for control are as discussed under bovine respiratory disease Overview of Bovine Respiratory Disease Complex Bovine respiratory disease (BRD), shipping fever pneumonia, or undifferentiated fever is a respiratory disease of cattle of multifactorial etiology with Mannheimia haemolytica and, less... read more . Immunization with modified live or killed virus vaccines generally provides adequate protection against clinical disease. Both IM and intranasal modified live virus vaccines are available; however, the IM types may cause abortion in pregnant cattle. The intranasal modified live virus vaccines can be used in pregnant cattle.

Modified live vaccines provide a longer duration of immunity and often are the vaccines of choice in feedlots where potential exposure to IBR virus is high. Breeding and replacement heifers and bulls should be immunized when 6–8 months old, before breeding, and yearly thereafter. Some recommend that young bulls not be vaccinated, because they may be discriminated against when sold for breeding if they have antibody titers. Feeder calves should be immunized preferably 2–3 weeks before entry into the feedlot or alternatively at arrival. Many feedlot veterinarians recommend a second vaccination when animals are reimplanted to provide good duration of immunity.

A number of western European countries have eradicated or are attempting to eradicate bovine herpesvirus 1 from their domestic cattle populations. Eradication of the virus is possible by a combination of serologic 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 can cause rhinotracheitis (IBR), infectious pustular vulvovaginitis, balanoposthitis, conjunctivitis, and abortion in cattle.

  • Bovine herpesvirus also causes a 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.

  • Antimicrobials are indicated to prevent and treat secondary bacterial pneumonias.

  • Bovine herpesvirus 1 can be controlled effectively with modified live virus vaccines.

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 the 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 bovine respiratory disease 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 tends to be high, and the case fatality rate can be 0%–20%.

Etiology of Bovine Respiratory Syncytial Virus

Bovine respiratory syncytial virus (BRSV) is an RNA virus classified as a pneumovirus in the Paramyxovirus family. This virus was named for its characteristic cytopathic effect: the formation of syncytial cells. In additional to cattle, sheep and goats can also be infected by respiratory syncytial viruses. Human respiratory syncytial virus (HRSV) is an important respiratory pathogen in infants and young children. Antigenic subtypes are known to exist for HRSV, and preliminary evidence suggests there may be antigenic subtypes of BRSV. BRSV is distributed worldwide, and the virus is ubiquitous in the cattle population.

Clinical Findings and Lesions of Bovine Respiratory Syncytial Virus

Common clinical signs in bovine respiratory syncytial virus include:

  • fever (40°–42°C [104°–108°F])

  • depression

  • decreased feed intake

  • increased respiratory rate

  • cough

  • nasal and lacrimal discharge

Dyspnea, possibly with open-mouthed breathing, may become pronounced in the later stages of the disease. 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 a fatal interstitial pneumonia.

Gross lesions include a diffuse interstitial pneumonia with subpleural and interstitial emphysema along with interstitial edema. These lesions are similar to and must be differentiated from other causes of interstitial pneumonia Parainfluenza-3 Virus Bovine herpesvirus 1 infections are widespread in the cattle population. In feedlot cattle, the respiratory form is most common. The viral infection alone is not life-threatening but predisposes... read more Parainfluenza-3 Virus . Bronchopneumonia of bacterial origin is usually present. Histologic 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 of Bovine Respiratory Syncytial Virus

  • Nasopharyngeal swabs

  • Transtracheal aspirate

  • PCR assay or immunohistochemistry

  • Paired serologic testing

A diagnosis of bovine respiratory syncytial virus requires laboratory confirmation. 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 the 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 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 may 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 of Bovine Respiratory Syncytial Virus

  • Antimicrobials

  • Supportive treatment

Treatment of bovine respiratory syncytial virus focuses on using antimicrobials to control the secondary bacterial pneumonia Bacterial Pneumonia in Cattle with Bovine Respiratory Disease Complex Mannheimia haemolytica serotype 1 is the bacterial pathogen most frequently isolated from the lungs of recently weaned feedlot cattle with bovine respiratory disease (BRD) and in dairy... read more Bacterial Pneumonia in Cattle with Bovine Respiratory Disease Complex . There is no specific treatment for the viral interstitial pneumonia. Supportive treatment and correction of dehydration may be necessary. Most animals will recover in several days without treatment.

General control and prevention are discussed under Enzootic Pneumonia of Calves Enzootic Pneumonia of Calves Enzootic pneumonia of calves is the most common respiratory disease seen in young dairy, veal, or beef calves. The disease is caused by a variety of viral and bacterial pathogens and environmental... read more . Killed and modified live virus vaccines are available and may decrease losses associated with BRSV; however, there is a paucity of field trials to evaluate the efficacy of these vaccines.

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 serology.

  • Antimicrobials may be used to control secondary bacterial pneumonia.

  • Modified live and inactivated vaccines are available, but efficacy has not been firmly established.

Parainfluenza-3 Virus

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 is usually associated with mild to subclinical infections. The most important role of PI-3 is to serve as an initiator that can lead to development of secondary bacterial pneumonia.

Clinical signs of parainfluenza-3 virus include pyrexia, cough, serous nasal and lacrimal discharge, increased respiratory rate, and increased breath sounds. The severity of clinical signs worsens 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 a concurrent bacterial bronchopneumonia.

Bovine Viral Diarrhea Virus

Bovine viral diarrhea virus Bovine Viral Diarrhea and Mucosal Disease Complex Bovine viral diarrhea/mucosal disease is a pestivirus infection of cattle and other ruminants. Infection leads to immunosuppression and can cause signs in multiple body systems in addition to... read more (BVDV) is an RNA virus classified as a pestivirus in the family Flaviviridae. The role of BVDV in BRD as a primary pathogen has been controversial, but it appears to be capable of inducing immunosuppression, which allows for 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 infections of the respiratory tract of calves.

General principles of control are discussed under Enzootic Pneumonia of Calves Enzootic Pneumonia of Calves Enzootic pneumonia of calves is the most common respiratory disease seen in young dairy, veal, or beef calves. The disease is caused by a variety of viral and bacterial pathogens and environmental... read more . Killed and modified live virus vaccines are available for IM administration. Recently, vaccines containing both the type I and type II genotypes have become available. Vaccination of cows before breeding with modified live virus vaccines is an important strategy to prevent the occurrence of persistently infected calves. Testing for persistently infected calves and removing them from the pen has been used as a strategy to decrease the risk of disease within feedlots in high-risk groups.

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 previously recognized. Bovine coronavirus may play a role in some outbreaks of calf pneumonia on pasture in beef cow-calf operations.

These viruses have a role similar to that of the 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.

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