Bovine Leukosis

Enzootic bovine leukosis is due to BLV, an exogenous C-type oncogenic retrovirus of the BLV-human T-lymphotropic virus group. BLV has a stable genome, does not cause chronic viremia, and has no preferred site of proviral integration. Despite the lack of preferred proviral integration sites, the tumors generated by the virus in a single individual are typically monoclonal and have a single integration site. The virus escapes the immune response by low levels of viral replication. It appears that replication is blocked at the transcriptional level; however, the mechanism is not completely understood.

The prevalence of BLV infection varies from country to country. Many European countries, Australia, and New Zealand have eradication programs in place that have led to negligible rates of BLV infection. Although voluntary control programs are in place in the US, prevalence is high compared with much of the rest of the world. The most recent surveys in the US estimate that 94.2% of dairy herds contain positive cows with approximately 46.5% of cows infected.1 In beef cattle, estimates are lower, with 38.7% of the herds infected and 10.3% of beef cattle carrying the virus. Prevalence tends to increase on dairies with increasing herd size; however, the converse is true in beef cattle. In general, the prevalence of viral infection increases with age.

Cattle are infected with BLV via the transfer of blood and blood products that contain infected lymphocytes. Once infected, cattle develop a lifelong antibody response, primarily to the gp51 envelope protein and the p24 capsid protein. B lymphocytes harbor the integrated provirus but rarely express viral proteins on their cell surface. The exact site of viral replication and expression that drives the immune response remains elusive.

Under experimental conditions, most routes of viral exposure can successfully transmit infection. However, many of these settings are unlikely to be encountered naturally. Many bodily fluids, including urine, feces, saliva, respiratory secretions, semen, uterine fluids, and embryos, have been examined for their ability to transmit BLV and are considered to be noninfectious. Only on rare occasion has virus been found in these fluids. Colostrum from BLV-positive cows contains virus and has been found to be infectious experimentally. However, colostrum also contains large amounts of antibody, and it is believed that the protective effects of colostral antibody outweigh the infectious potential when colostrum is administered in a normal fashion.

Most BLV transmission is horizontal. Close contact between BLV-negative and BLV-positive cattle is thought to be a risk factor. Many common farm practices have been implicated in viral transmission, including tattooing, dehorning, rectal palpation, injections, and blood collection. Vectors such as tabanids and other large biting flies also may transmit the virus. Vertical transmission may occur transplacentally from an infected dam to the fetus or postpartum from the dam to the calf via ingestion of infected colostrum. Any material that is blood contaminated or lymphocyte rich has the potential to infect animals with BLV.

There are three main outcomes in cattle infected with bovine leukosis virus. Most animals remain persistently infected with no outward clinical signs of infection. Approximately 29% of BLV-infected cattle develop persistent lymphocytosis, while < 5% of BLV-infected cattle develop lymphosarcoma.

Persistent lymphocytosis is sometimes referred to as a preneoplastic syndrome; however, there is no convincing evidence that affected cattle have an increased risk of developing lymphosarcoma. The lymphocytes present in persistent lymphocytosis are not neoplastic, although they may have mild reactive changes consistent with normal blood smears in cattle. Persistent lymphocytosis is considered a benign condition associated with BLV infection. For this reason, it is often overlooked.

However, these cows may serve as a reservoir of infection. The increased lymphocyte count is attributed to a 45-fold increase of infected CD5⁺ and a 99-fold increase in infected CD5⁻ B cells. It has been suggested that cows with persistent lymphocytosis may be at greater risk of passing BLV infection on to their calves in utero and may show decreased milk production and alteration of milk components.

Lymphosarcoma rarely occurs in animals < 2 years old and is most common in the 4- to 8-year-old age group. Lymphosarcoma, including both sporadic and enzootic forms, is one of the main causes of condemnation of adult dairy cows at slaughter in the US.

Uterine wall and caruncle, cow

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Courtesy of Dr. Dusty Nagy.

Thymic lymphosarcoma

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Courtesy of Dr. Dusty Nagy.

Cardiac lymphosarcoma, cow

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Courtesy of Dr. Dusty Nagy.

Clinical signs associated with development of lymphosarcoma are highly variable, because the affected organ(s) will dictate the predominant clinical signs.

Juvenile lymphosarcoma is often characterized by a sudden onset of diffuse lymphoid hyperplasia with or without visceral organ involvement. Weight loss, fever, tachycardia, dyspnea, bloat, and posterior paresis have all been described with this form of lymphosarcoma. Profound lymphocytosis (> 50,000/mcL) often accompanies this fatal form of bovine lymphosarcoma. Thymic lymphosarcoma may involve the cervical or intrathoracic thymus, or both.

Clinical signs associated with this form of lymphosarcoma depend heavily on the location and size of the tumor. A cervical swelling may be evident. Dyspnea, bloat, jugular distention, tachycardia, anterior edema, and fever have been documented. The affected cell population is an immature, poorly differentiated lymphocyte. Cutaneous lymphosarcoma presents as cutaneous plaques, 1–5 cm in diameter, on the neck, back, rump, and thighs. Regional lymph nodes may also be enlarged. This form of lymphosarcoma may undergo spontaneous remission; however, relapses may occur.

• Serologic testing

• Cytology or histologic examination of biopsy samples

Lymphosarcoma is often included on the differential diagnosis list for many diseases because of the wide range of clinical findings. Viral infection is diagnosed by serology or virology, persistent lymphocytosis is identified by hematology, and neoplastic tumors are identified by histologic examination of biopsies. Positive serology or virology testing for BLV confirms viral infection but not the presence of lymphosarcoma.

Serologic testing by means of ELISA is the most common and reliable way to diagnose infection with BLV. Serology is unreliable in calves that have ingested colostrum from BLV-positive cows because of the passive acquisition of maternal antibodies that typically wane by 4–6 months old. PCR is a sensitive and specific assay for diagnosis of BLV infection in peripheral blood lymphocytes. This test can identify proviral DNA of BLV in the lymphocytes of infected animals and differentiate positive from negative calves in the presence of maternal antibodies.

The diagnosis of lymphosarcoma must be made by cytology or histopathology. Cytologic diagnosis is sometimes difficult because of the frequency of blood contamination of the aspirates.

• No viable treatment

• Limit transfer of infected lymphocytes from one cow to another

There is no treatment for viral infection or for lymphosarcoma in cattle, although parenteral corticosteroids can transiently decrease the severity of clinical signs. Eradication programs have been developed; however, success has been variable, primarily because of the expense and high prevalence of infection among cattle in the US relative to the economic cost of disease. The most commonly recommended eradication protocol is as follows:

• identify infected animals using a serologic test

• cull seropositive animals immediately

• retest the herd in 30–60 days

• use PCR assay to test young calves and as a complementary test to clarify test results in herds with a low prevalence of infection

• repeat testing and cull until the entire herd tests negative

Testing is then repeated every 6 months. The herd is declared free when there have been no positive tests for 2 years. Additions to the herd should have two negative tests 30 and 60 days before arrival.

When test and cull programs are economically untenable, test and segregation programs have been recommended but are rarely implemented. These programs necessitate running two completely separate operations and require additional resources, including money, time, and available workforce.

Eliminating the exposure to blood from infected animals to naive animals is the cornerstone of prevention protocols for bovine leukosis. In calves, feeding colostrum from seronegative cows is often advocated. However, most epidemiologic evidence suggests that the protective effect of colostral antibody outweighs the risk of infections, particularly in high-prevalence herds. The replacement of whole milk feeding with high-quality milk replacer may also be considered. Bloody milk should never be fed to calves.

Cautery or other bloodless methods of dehorning should be used. Equipment used for castration, tattooing, or implanting should be adequately cleaned and disinfected between animals.

Transmission can be decreased in adult cattle by changing rectal sleeves in between cows. Artificial insemination or embryo transfer (using negative recipients) may limit transmission. In beef herds, the use of a negative bull may limit transmission; however, natural service is an uncommon method of viral transmission unless breeding is traumatic or the bull has vesiculitis or another reproductive disease that may lead to semen contamination with blood or infected lymphocytes.

Additional recommendations include:

• disinfecting equipment that has come in contact with blood or body tissue

• using single-use, disposable needles for blood collection and IM injections (It is preferable to use single-use disposable needles for vaccination; however, the risk of transmitting BLV virus via subcutaneous vaccination is low.)

• cleaning handling facilities between animals when contaminated with blood

• cleaning maternity and calving pens after each animal to prevent contaminated fluids from coming into contact with the next animal

• controlling flies to help minimize the potential for tabanid-associated transmission, although this route of infection is considered to be minor

• screening blood donors carefully; transfusions and vaccines containing blood, such as those used for babesiosis and anaplasmosis, are particularly potent ways to transmit the disease

In veterinary medicine, bovine leukemia virus is not typically thought of as zoonotic. However, there is research within demonstrating viral DNA in human lung, mammary, and buffy coat cells.1-3 There is interest in the virus’s ability to potentially affect regulatory pathways and oncogenesis in human cancer. There is some evidence that the virus is more commonly found in malignant vs benign human tissue samples.4 One study looking at risk factors for human infection found ingesting unpasteurized dairy products such as milk and yogurt to be a risk. Ingestion of other products, such as cheese and commercial milk, as well as contact with cows, were not considered to be risk factors.4 Although the virus has been detected in people, and some associations have been made, there is considerable knowledge needed to clarify the risk of animal interactions with people and of BLV as a human zoonosis.  

• Bovine leukemia virus (BLV). Animal and Plant Health Inspection Service. USDA. Updated March 5, 2021.