Peripheral nerve protein, P0, as a potential receptor for Theiler's murine encephalomyelitis virus

Theiler's murine encephalomyelitis virus (TMEV) belongs the family Picornaviridae. TMEV not only replicates in the gastrointestinal tract but also spreads to the central nervous system (CNS) either by a hematogenous or a neural pathway during natural infection. The DA strain of TMEV infects neurons during the acute phase, and glial cells and macrophages during the chronic phase, leading to a demyelinating disease similar to multiple sclerosis. Different virus-host receptor interactions in the peripheral and the neuronal cells could explain the pathways of viral spread from the peripheral to the CNS and neurons to glial cells. However, the receptor for TMEV remains unknown. P0 protein, a 28-31 kD glycoprotein, belongs to the immunoglobulin superfamily and constitutes 50% of the total myelin protein in the peripheral nerve. Other picornaviruses use members of the immunoglobulin superfamily as receptors. Thus we hypothesized P0 protein could act as a receptor for TMEV. In a virus overlay assay, radiolabeled TMEV bound to a 28-30 kD protein from the peripheral nerve of wild-type C57BL/6, but no binding was found in the peripheral nerve from P0-knockout mice. TMEV replicated fourfold higher in P0-transfected BW5147.G.1.4 cells than in mock-transfected cells. The increase in virus replication in the P0-transfected cell line was blocked by preincubation of the cells with anti-P0 antibody. A virus binding study showed that TMEV bound to P0-transfected cells but not to mock-transfected cells. The use of the P0 protein in Schwann cells as a receptor may be one mechanism by which TMEV spreads from the gastrointestinal tract to the CNS.