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News Article

Novel control method against Bovine leukemia virus infection


Combined drug treatment effective against BLV infection, pilot study shows

By combining an immune checkpoint inhibitor with an enzyme inhibitor, researchers have managed to reduce Bovine leukemia virus (BLV) levels in infected cows.

BLV infection is prevalent in many countries, including Japan, with seroprevalence in Japanese cattle on the rise due to the lack of an effective treatment or vaccine.

In a previous study, a research team led by Satoru Konnai of Hokkaido University demonstrated that prostaglandin E2 (PGE2) inhibits the Th1 response and induces the expression of PD-L1 in cattle, contributing to the progression of Johne’s disease. The combined treatment with an anti–PD-L1 (anti-programmed death-ligand 1) Ab and a COX-2 inhibitor enhanced M. avium subsp. paratuberculosis–specific Th1 responses in vitro. Since few studies exist on the association between PGE2 and BLV infection, the present study was undertaken to analyse the kinetics of PGE2 in BLV infection, the association of PGE2 with disease progression, as well as the anti-viral effects of a COX-2 inhibitor in vivo and in vitro

The results, described in an open access paper in The Journal of Immunology, showed that blood PGE2 levels increased in BLV-infected cows as the disease progressed. The COX-2 inhibitor, meloxicam, which blocks the production of PGE2, activated an immune response against BLV in cultured immune cells; when combined with the anti-PD-L1 Ab boosted the immune activation effect. Furthermore, cows administered the COX-2 inhibitor showed reduced viral loads, demonstrating its antiviral effect in the animals. Administering both the COX-2 inhibitor and anti-PD-L1 Ab led to reduced viral loads in advanced stage cows.

The researchers plan to conduct additional experiments using large numbers of infected cattle to confirm the efficacy of the treatment.

Prostaglandin E2–Induced Immune Exhaustion and Enhancement of Antiviral Effects by Anti–PD-L1 Antibody Combined with COX-2 Inhibitor in Bovine Leukemia Virus Infection. Sajiki Y, Konnai S, Okagawa T, Nishimori A, Maekawa N, Goto S, Watari K, Minato E, Kobayashi A, Kohara J, Yamada S, Kaneko MK, Kato Y, Takahashi H, Terasaki N, Takeda A,  Yamamoto K, Toda M, Suzuki Y, Murata S, Ohashi K. Journal of Immunology, ji1900342; published online 31 July 2019, DOI: https://doi.org/10.4049/jimmunol.1900342 (open access)

Article details

  • Date
  • 12 August 2019
  • Source
  • Hokkaido University
  • Subject(s)
  • Veterinary medicine