Bovine Leukosis

Study on bovine leukosis

 

   Bovine leukemia virus (BLV: family, Retroviridae; subfamily, Orthoretrovirinae; genus, Deltaretrovirus) is the causative agent of enzootic bovine leukosis (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 and more than 4,500 cases have been reported in 2025. 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 50 years: epidemiological survey of BLV infection and leukemia cases, search for tumor-associated antigens, mechanisms of disease progression and antiviral immunity, analysis of proviral integration sites and development of vaccine candidate. Currently, we have three approaches to develop effective methods for the prevention and control of bovine leukemia based on the results from our research activities.

 

1. Development of novel risk assessment method for EBL onset based on the clonality analysis of proviral integration sites of BLV-infected cells

   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. Development of novel therapeutic method based on immunological analysis of BLV　infection

   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. Investigation of mechanism 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.

 

 

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• Research, Top

• Theme 1.  Immune checkpoints

• Theme 2.  Ticks and Poultry Red mites

• Theme 3.  Bovine leukosis

• Theme 4.  Marek's disease
• Theme 5.  Probiotics