Exploring the Role of Platelets in Virus-Induced Inflammatory Demyelinating Disease and Myocarditis

• Published in: International journal of molecular sciences Vol. 25; no. 6; p. 3460
• Main Authors: Ahmad, Ijaz, Omura, Seiichi, Sato, Fumitaka, Park, Ah-Mee, Khadka, Sundar, Gavins, Felicity N E, Tanaka, Hiroki, Kimura, Motoko Y, Tsunoda, Ikuo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2024; MDPI
• Subjects: Analysis; Animals; bioinformatics analysis; Blood platelets; Cardiomyocytes; Central Nervous System - metabolism; Chronic Disease; dilated cardiomyopathy; Encephalomyelitis; Epstein-Barr virus; Gene expression; Genes; glycoprotein Ib α chain; Glycoproteins; Health aspects; Hepatitis C; Histocompatibility Antigens Class I - metabolism; Humans; Immune response; Immunity; Infection; Infections; Inflammation; Inflammatory diseases; Interferon; Ligands; Mice; Multiple sclerosis; Multiple Sclerosis - metabolism; Myocarditis; Myocarditis - etiology; Myocarditis - metabolism; neuroinflammatory disease; Pathogenesis; Pathogens; Pathology; regulation of gene expression; RNA sequencing analyses; Scientific equipment and supplies industry; Severe acute respiratory syndrome coronavirus 2; Spinal cord; Spleen; T cell receptors; Viral antigens; Viral infections; United States; Japan; RNA sequencing analyses; picornavirus infections; regulation of gene expression; bioinformatics analysis; neuroinflammatory disease; dilated cardiomyopathy; glycoprotein Ib α chain
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25063460

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.