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

Theiler's murine encephalomyelitis virus (TMEV) belongs the family Picornav iridae. TMEV not only replicates in the gastrointestinal tract but also spr eads to the central nervous system (CNS) either by a hematogenous or a neur al 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, Di fferent virus-host receptor interactions in the peripheral and the neuronal cells could explain the pathways of viral spread from the peripheral to th e CNS and neurons to glial cells. However, the receptor for TMEV remains un known, PO protein, a 28-31 kD glycoprotein, belongs to the immunoglobulin s uperfamily and constitutes 50% of the total myelin protein in the periphera l nerve. Other picornaviruses use members of the immunoglobulin superfamily as receptors. Thus we hypothesized PO protein could act as a receptor for TMEV. In a virus overlay assay, radiolabeled TMEV bound to a 28-30 kD prote in from the peripheral nerve of wild-type C57BL/6, but no binding was found in the peripheral nerve from PO-knockout mice. TMEV replicated fourfold hi gher in PO-transfected BW5147.G.1.4 cells than in mock-transfected cells. T he increase in virus replication in the PO-transfected cell line was blocke d by preincubation of the cells with anti-PO antibody. A virus binding stud y showed that TMEV bound to PO-transfected cells but not to mock-transfecte d cells. The use of the PO protein in Schwann cells as a receptor may be on e mechanism by which TMEV spreads from the gastrointestinal tract to the CN S.