A TLR7 agonist activates bovine Th1 response and exerts antiviral activity against bovine leukemia virus

Yamato Sajiki; Satoru Konnai; Tomohiro Okagawa; Naoya Maekawa; Hayato Nakamura; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi

doi:10.1016/j.dci.2020.103847

A TLR7 agonist activates bovine Th1 response and exerts antiviral activity against bovine leukemia virus

Dev Comp Immunol. 2021 Jan:114:103847. doi: 10.1016/j.dci.2020.103847. Epub 2020 Sep 2.

Authors

Yamato Sajiki¹, Satoru Konnai², Tomohiro Okagawa³, Naoya Maekawa⁴, Hayato Nakamura⁵, Yukinari Kato⁶, Yasuhiko Suzuki⁷, Shiro Murata⁸, Kazuhiko Ohashi⁹

Affiliations

¹ Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan. Electronic address: y.sajiki@vetmed.hokudai.ac.jp.
² Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan; Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan. Electronic address: konnai@vetmed.hokudai.ac.jp.
³ Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan. Electronic address: okagawa@vetmed.hokudai.ac.jp.
⁴ Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan. Electronic address: maekawa@vetmed.hokudai.ac.jp.
⁵ Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan. Electronic address: btbw-h314@eis.hokudai.ac.jp.
⁶ Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan; New Industry Creation Hatchery Center, Tohoku University, Sendai, 980-8575, Japan. Electronic address: yukinarikato@med.tohoku.ac.jp.
⁷ Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan; Division of Bioresources, Research Center for Zoonosis Control, Hokkaido University, Sapporo, 001-0019, Japan. Electronic address: suzuki@czc.hokudai.ac.jp.
⁸ Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan; Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan. Electronic address: murata@vetmed.hokudai.ac.jp.
⁹ Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan; Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan. Electronic address: okazu@vetmed.hokudai.ac.jp.

PMID: 32888966
DOI: 10.1016/j.dci.2020.103847

Abstract

Bovine leukemia virus (BLV) infection is a bovine chronic infection caused by BLV, a member of the genus Deltaretrovirus. In this study, we examined the immunomodulatory effects of GS-9620, a toll-like receptor (TLR) 7 agonist, in cattle (Bos taurus) and its therapeutic potential for treating BLV infection. GS-9620 induced cytokine production in peripheral blood mononuclear cells (PBMCs) as well as CD80 expression in CD11c⁺ cells and increased CD69 and interferon (IFN)-γ expressions in T cells. Removing CD11c⁺ cells from PBMCs decreased CD69 expression in T cells in the presence of GS-9620. These results suggest that TLR7 agonism promotes T-cell activation via CD11c⁺ cells. Analyses using PBMCs from BLV-infected cattle revealed that TLR7 expression in CD11c⁺ cells was upregulated during late-stage BLV infection. Furthermore, GS-9620 increased IFN-γ and TNF-α production and inhibited syncytium formation in vitro, suggesting that GS-9620 may be used to treat BLV infection.

Keywords: Anti-PD-L1 antibody; Bovine leukemia virus; CD11c(+) cell; Cattle; T cell; TLR7 agonist.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD / metabolism
Antigens, Differentiation, T-Lymphocyte / metabolism
Antiviral Agents / pharmacology
Antiviral Agents / therapeutic use*
CD11c Antigen / metabolism
Cattle
Cells, Cultured
Enzootic Bovine Leukosis / drug therapy
Enzootic Bovine Leukosis / immunology*
Interferon-gamma / metabolism
Lectins, C-Type / metabolism
Leukemia Virus, Bovine / physiology*
Lymphocyte Activation
Pteridines / pharmacology
Pteridines / therapeutic use*
Th1 Cells / immunology*
Toll-Like Receptor 7 / agonists*
Tumor Necrosis Factor-alpha / metabolism
Viral Load

Substances

Antigens, CD
Antigens, Differentiation, T-Lymphocyte
Antiviral Agents
CD11c Antigen
CD69 antigen
Lectins, C-Type
Pteridines
Toll-Like Receptor 7
Tumor Necrosis Factor-alpha
Interferon-gamma
vesatolimod