Immunological role of platelets in Theiler's virus-induced  inflammatory demyelinating disease and myocarditis
Platelets have been immunologically associated with viral and immune-mediated diseases such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Experimental autoim-mune encephalomyelitis (EAE). However, the role of platelets in Theiler's murine encephalo-myelitis virus (TMEV)-induced myocarditis and inflammatory demyelination disease (IDD) is still unknown. We determine whether platelets were associated with TMEV infection and whether glycoprotein Ib alpha chain (GPIba/CD42b) antibody injection could affect the pathogenicity of TMEV-induced myocarditis and TMEV-IDD. We conducted a mechanistic experiment by injecting TMEV-infected mice with the anti-GPIba antibodies 0 and 5 days p.i. (“Early” group) or 18 and 22 days p.i. (“Late” group). Using in silico and in vivo approaches, we found platelets and platelet-related genes were associated with TMEV infection. Platelet depletion in Early and Late mice reduced fibrotic area in the heart, inflammatory demyelinating lesions with lower viral persistence in the CNS and altered antiviral antibody responses. Thus, platelets contribute to the pathogenesis of TMEV infection by promoting fibrosis and CNS inflammation. Platelet-depletion treatment might open new therapeutic approaches for TMEV-induced myocarditis and TMEV-IDD. Overall design: We aimed to determine the roles of platelets in the pathogenesis of multiple sclerosis and viral myocarditis, using a mouse model induced by Theiler's murine encephalomyelitis virus (TMEV) infection. We conducted the RNA sequencing analyses of the spleen and platelet samples from female SJL/J mice infected with TMEV (2 × 10^5 plaque forming units) intracerebrally on 4, 7, and 35 days post infection. As a control, we prepared age-matched female SJL/J mice injected with PBS intracerebrally.