Data Availability Statement:
The data generated for this study can be found in the GEO at the NCBI (accession no. GSE253385, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE253385 (accessed on 15 March 2024)).Supplementary Materials:
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/ijms25063460/s1 .Theiler’s murine encephalomyelitis virus (TMEV) infection has been used as a mouse model for two virus-induced organ-specific immune-mediated diseases. TMEV-induced demyelinating disease (TMEV-IDD) in the central nervous system (CNS) is a chronic inflammatory disease with viral persistence and an animal model of multiple sclerosis (MS) in humans. TMEV infection can also cause acute myocarditis with viral replication and immune cell infiltration in the heart, leading to cardiac fibrosis. Since platelets have been reported to modulate immune responses, we aimed to determine the role of platelets in TMEV infection. In transcriptome analyses of platelets, distinct sets of immune-related genes, including major histocompatibility complex (MHC) class I, were up- or downregulated in TMEV-infected mice at different time points. We depleted platelets from TMEV-infected mice by injecting them with platelet-specific antibodies. The platelet-depleted mice had significantly fewer viral antigen-positive cells in the CNS. Platelet depletion reduced the severities of TMEV-IDD and myocarditis, although the pathology scores did not reach statistical significance. Immunologically, the platelet-depleted mice had an increase in interferon (IFN)-γ production with a higher anti-TMEV IgG2a/IgG1 ratio. Thus, platelets may play roles in TMEV infection, such as gene expression, viral clearance, and anti-viral antibody isotype responses.This work is supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan, through the Monbukagakusho (MEXT, 2021-2025) Scholarship (I.A.), Grant-in Aid for Scientific Research KAKENHI from the Japan Society for the Promotion of Science (JSPS) (JP22K07527 (S.O.), JP23K06493 (F.S.), JP21K07167 (H.T.), and JP22K18378 and JP23K08901 (I.T.)), Novartis Pharma Research Grants (S.O. and I.T.), the Royal Society Wolfson Foundation (RSWF\R3\183001, (F.N.E.G.)), the Hokkaido Lawyer Association for Hepatitis B (Orange funding) (H.T.), and Hokkaido Organization for Translational Research (A seeds) (H.T.)
