Foot-and-mouth disease virus VP1 target the MAVS to inhibit type-I interferon signaling and VP1 E83K mutation results in virus attenuation

Pathum Ekanayaka; Seo-Yong Lee; Thilina U B Herath; Jae-Hoon Kim; Tae-Hwan Kim; Hyuncheol Lee; Kiramage Chathuranga; W A Gayan Chathuranga; Jong-Hyeon Park; Jong-Soo Lee

doi:10.1371/journal.ppat.1009057

Foot-and-mouth disease virus VP1 target the MAVS to inhibit type-I interferon signaling and VP1 E83K mutation results in virus attenuation

PLoS Pathog. 2020 Nov 24;16(11):e1009057. doi: 10.1371/journal.ppat.1009057. eCollection 2020 Nov.

Authors

Pathum Ekanayaka¹, Seo-Yong Lee^{1

2

3}, Thilina U B Herath¹, Jae-Hoon Kim⁴, Tae-Hwan Kim^{1

5}, Hyuncheol Lee^{1

6}, Kiramage Chathuranga¹, W A Gayan Chathuranga¹, Jong-Hyeon Park², Jong-Soo Lee¹

Affiliations

¹ College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
² Animal and Plant Quarantine Agency, Gyeongsangbuk-do, Republic of Korea.
³ FVC, Gyeongsangbuk-do, Republic of Korea.
⁴ Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology (UST), Daejeon, Republic of Korea.
⁵ Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
⁶ California Institute for Quantitative Biosciences, University of California, Berkeley, California, United States of America.

Abstract

VP1, a pivotal capsid protein encoded by the foot-and-mouth disease virus (FMDV), plays an important role in receptor-mediated attachment and humoral immune responses. Previous studies show that amino acid changes in the VP1 protein of cell culture-adapted strains of FMDV alter the properties of the virus. In addition, FMDV VP1 modulates host IFN signal transduction. Here, we examined the ability of cell culture-adapted FMDV VP1(83K) and wild-type FMDV VP1(83E) to evade host immunity by blocking mitochondrial antiviral signaling protein (MAVS)/TNF Receptor Associated Factor 3 (TRAF3) mediated cellular innate responses. Wild-type FMDV VP1(83E) interacted specifically with C-terminal TRAF3-binding site within MAVS and this interaction inhibited binding of TRAF3 to MAVS, thereby suppressing interferon-mediated responses. This was not observed for cell culture-adapted FMDV VP1(83K). Finally, chimeric FMDV harboring VP1(83K) showed very low pathogenicity in pigs. Collectively, these data highlight a critical role of VP1 with respect to suppression of type-I IFN pathway and attenuation of FMDV by the E83K mutation in VP1.

Publication types

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

MeSH terms

Amino Acid Substitution
Animals
Capsid Proteins / genetics*
Capsid Proteins / metabolism
Foot-and-Mouth Disease / immunology
Foot-and-Mouth Disease / virology*
Foot-and-Mouth Disease Virus / genetics*
Foot-and-Mouth Disease Virus / immunology
Immunity, Innate
Interferons / metabolism
Mutation
Protein Binding
Signal Transduction*
TNF Receptor-Associated Factor 3 / genetics
TNF Receptor-Associated Factor 3 / metabolism

Substances

Capsid Proteins
TNF Receptor-Associated Factor 3
VP1 protein, Foot-and-mouth disease virus
Interferons

Grants and funding

This work was supported by the Ministry for Food, Agriculture, Forestry and Fisheries (https://www.mafra.go.kr/english/index.do) (Grant No. 318039-3, grant recipient: JSL), National Research Foundation (http://www.nrf.re.kr/eng/index) (Grant No. 2018M3A9H4079660, 2018M3A9H4078703, 2019R1A2C2008283, grant recipient: JSL) and Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (https://www.kribb.re.kr/eng2/main/main.jsp) (KGM9942011, grant recipient: JSL), Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.