Study on bovine leukemia

 

   Bovine leukemia virus (BLV: family, Retroviridae; subfamily, Orthoretrovirinae; genus, Deltaretrovirus) is the causative agent of enzootic bovine leukemia (EBL), which manifests as B-cell lymphomas in 1%–5% of BLV-infected cattle. Although has been eradicated in some European countries, EBL is still prevalent worldwide, including Japan where the number of EBL cases has been increasing recently. A nationwide survey in Japan conducted from 2009 to 2011 indicated high seroprevalence of BLV in both dairy and beef cattle (40.9% and 28.7%, respectively). To date, no vaccine and therapeutic method are available for the prevention of this disease.

   We started studies on BLV infection in 1970s, and have conducted many research activities over the past 40 years: epidemiological survey of BLV infection and leukemia cases, search for tumor-associated antigens, mechanism(s) of disease progression and antiviral immunity, and development of vaccine candidate. Currently, we have three approaches to develop effective method(s) for the prevention and control of bovine leukemia based on the results from our research activities.

 

1. Development of novel therapeutic method(s) based on immunological analysis of BLV infection

   Progressive exhaustion of T-cell functions is considered to facilitate disease progression of BLV infection. Our previous studies unveiled the mechanisms of T-cell exhaustion mediated by immune checkpoint molecules or regulatory T cells in BLV infection. We are currently conducting pilot clinical trials of molecular targeted drugs to test their immunomodulatory and therapeutic effects on BLV-infected cattle.

 

2. Investigation of mechanism(s) of tumor development based on phenotypic analysis of bovine leukemia

   EBL is characterized by systemic B-cell lymphoma associated with BLV infection after a long latent period. Although EBL has been demonstrated to occur predominantly in adult cattle of >3–5 years, suspicious cases of the EBL onset in juvenile cattle were recently reported in Japan. We thus performed immunophenotypic analysis of clinical samples from cattle with leukemia, and identified novel characteristics of EBL, including early onset in juvenile animals. These findings should contribute to a better understanding of the mechanism underlying tumor development in BLV infection.

 

3. Establishment of control measure for bovine leukemia based on risk analysis of viral transmission

   We annually test around 3,000–4,000 heads of clinical samples and diagnose BLV infection. The results of the diagnosis provide helpful information to improve farm management, such as the introduction of the routine test for newly introduced cattle into farm and newborn calves, isolation and priority culling of the infected animals, etc. Additionally, we are verifying several approaches toward herd eradication or control of BLV infection at model farms.