Application of the Luminescence Syncytium Induction Assay to Identify Chemical Compounds That Inhibit Bovine Leukemia Virus Replication

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2023 Jan 21

PMID 36680045

Authors

Hirotaka Sato

Jun-Na Fukui

Hiroyuki Hirano

Hiroyuki Osada

Yutaka Arimura

Michiaki Masuda

Yoko Aida

Affiliations

Soon will be listed here.

Abstract

Bovine leukemia virus (BLV) infection causes endemic bovine leukemia and lymphoma, resulting in lower carcass weight and reduced milk production by the infected cattle, leading to economic losses. Without effective measures for treatment and prevention, high rates of BLV infection can cause problems worldwide. BLV research is limited by the lack of a model system to assay infection. To overcome this, we previously developed the luminescence syncytium induction assay (LuSIA), a highly sensitive and objectively quantifiable method for visualizing BLV infectivity. In this study, we applied LuSIA for the high-throughput screening of drugs that could inhibit BLV infection. We screened 625 compounds from a chemical library using LuSIA and identified two that markedly inhibited BLV replication. We then tested the chemical derivatives of those two compounds and identified BSI-625 and -679 as potent inhibitors of BLV replication with low cytotoxicity. Interestingly, BSI-625 and -679 appeared to inhibit different steps of the BLV lifecycle. Thus, LuSIA was applied to successfully identify inhibitors of BLV replication and may be useful for the development of anti-BLV drugs.

Citing Articles

The Global Epidemiology of Bovine Leukemia Virus: Current Trends and Future Implications.

Lv G, Wang J, Lian S, Wang H, Wu R Animals (Basel). 2024; 14(2).

PMID: 38254466 PMC: 10812804. DOI: 10.3390/ani14020297.

Application of the Luminescence Syncytium Induction Assay to Identify Chemical Compounds That Inhibit Bovine Leukemia Virus Replication.

Sato H, Fukui J, Hirano H, Osada H, Arimura Y, Masuda M Viruses. 2023; 15(1).

PMID: 36680045 PMC: 9861517. DOI: 10.3390/v15010004.

References

Hammer S, Squires K, Hughes M, Grimes J, Demeter L, Currier J . A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997; 337(11):725-33. DOI: 10.1056/NEJM199709113371101. View

Sato H, Watanuki S, Murakami H, Sato R, Ishizaki H, Aida Y . Development of a luminescence syncytium induction assay (LuSIA) for easily detecting and quantitatively measuring bovine leukemia virus infection. Arch Virol. 2018; 163(6):1519-1530. DOI: 10.1007/s00705-018-3744-7. View

Bai L, Borjigin L, Sato H, Takeshima S, Asaji S, Ishizaki H . Kinetic Study of BLV Infectivity in BLV Susceptible and Resistant Cattle in Japan from 2017 to 2019. Pathogens. 2021; 10(10). PMC: 8537920. DOI: 10.3390/pathogens10101281. View

Rodriguez S, Florins A, Gillet N, de Brogniez A, Sanchez-Alcaraz M, Boxus M . Preventive and therapeutic strategies for bovine leukemia virus: lessons for HTLV. Viruses. 2011; 3(7):1210-48. PMC: 3185795. DOI: 10.3390/v3071210. View

Lo C, Borjigin L, Saito S, Fukunaga K, Saitou E, Okazaki K . BoLA-DRB3 Polymorphism is Associated with Differential Susceptibility to Bovine Leukemia Virus-Induced Lymphoma and Proviral Load. Viruses. 2020; 12(3). PMC: 7150773. DOI: 10.3390/v12030352. View

Kerkhofs P, Heremans H, Burny A, Kettmann R, Willems L . In vitro and in vivo oncogenic potential of bovine leukemia virus G4 protein. J Virol. 1998; 72(3):2554-9. PMC: 109563. DOI: 10.1128/JVI.72.3.2554-2559.1998. View

Barez P, de Brogniez A, Carpentier A, Gazon H, Gillet N, Gutierrez G . Recent Advances in BLV Research. Viruses. 2015; 7(11):6080-8. PMC: 4664998. DOI: 10.3390/v7112929. View

Nakatsuchi A, Watanuki S, Borjigin L, Sato H, Bai L, Matsuura R . Polymorphism Controls Proviral Load and Infectivity of Bovine Leukemia Virus (BLV) in Milk. Pathogens. 2022; 11(2). PMC: 8879029. DOI: 10.3390/pathogens11020210. View

Nekouei O, VanLeeuwen J, Sanchez J, Kelton D, Tiwari A, Keefe G . Herd-level risk factors for infection with bovine leukemia virus in Canadian dairy herds. Prev Vet Med. 2015; 119(3-4):105-13. DOI: 10.1016/j.prevetmed.2015.02.025. View

10.

Murakami H, Murakami-Kawai M, Kamisuki S, Hisanobu S, Tsurukawa Y, Uchiyama J . Specific antiviral effect of violaceoid E on bovine leukemia virus. Virology. 2021; 562:1-8. DOI: 10.1016/j.virol.2021.06.010. View

11.

Bai L, Sato H, Kubo Y, Wada S, Aida Y . CAT1/SLC7A1 acts as a cellular receptor for bovine leukemia virus infection. FASEB J. 2019; 33(12):14516-14527. PMC: 6894071. DOI: 10.1096/fj.201901528R. View

12.

DeVincenzo J, Tait D, Efthimiou J, Mori J, Kim Y, Thomas E . A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein. Antimicrob Agents Chemother. 2019; 64(2). PMC: 6985722. DOI: 10.1128/AAC.01884-19. View

13.

Zhang , Chung , OLDENBURG . A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J Biomol Screen. 2000; 4(2):67-73. DOI: 10.1177/108705719900400206. View

14.

Aboukamar W, Elhenawy A, Elmehankar M, Elzoheiry M, El-Gamal R, Elabbasy L . Activity of isoflavone biochanin A in chronic experimental toxoplasmosis: impact on inflammation. Parasitol Res. 2022; 121(8):2405-2414. PMC: 9279236. DOI: 10.1007/s00436-022-07571-y. View

15.

Watanuki S, Takeshima S, Borjigin L, Sato H, Bai L, Murakami H . Visualizing bovine leukemia virus (BLV)-infected cells and measuring BLV proviral loads in the milk of BLV seropositive dams. Vet Res. 2019; 50(1):102. PMC: 6884895. DOI: 10.1186/s13567-019-0724-1. View

16.

Perach M, Hizi A . Catalytic features of the recombinant reverse transcriptase of bovine leukemia virus expressed in bacteria. Virology. 1999; 259(1):176-89. DOI: 10.1006/viro.1999.9761. View

17.

Arabyan E, Hakobyan A, Kotsinyan A, Karalyan Z, Arakelov V, Arakelov G . Genistein inhibits African swine fever virus replication in vitro by disrupting viral DNA synthesis. Antiviral Res. 2018; 156:128-137. PMC: 7127377. DOI: 10.1016/j.antiviral.2018.06.014. View

18.

Ikebuchi R, Konnai S, Okagawa T, Yokoyama K, Nakajima C, Suzuki Y . Blockade of bovine PD-1 increases T cell function and inhibits bovine leukemia virus expression in B cells in vitro. Vet Res. 2013; 44:59. PMC: 3726328. DOI: 10.1186/1297-9716-44-59. View

19.

Tohma D, Tajima S, Kato F, Sato H, Kakisaka M, Hishiki T . An estrogen antagonist, cyclofenil, has anti-dengue-virus activity. Arch Virol. 2018; 164(1):225-234. DOI: 10.1007/s00705-018-4079-0. View

20.

Takeshima S, Ohno A, Aida Y . Bovine leukemia virus proviral load is more strongly associated with bovine major histocompatibility complex class II DRB3 polymorphism than with DQA1 polymorphism in Holstein cow in Japan. Retrovirology. 2019; 16(1):14. PMC: 6524304. DOI: 10.1186/s12977-019-0476-z. View