Differentiation of M1 myeloid precursor cells into macrophages results in binding and infection by Theiler's murine encephalomyelitis virus and apoptosis

Infection of susceptible mouse strains with BeAn, a less virulent strain of Theiler's murine encephalomyelitis virus (TMEV), results in immune system- mediated demyelinating lesions in the central nervous system (CNS) similar to those in multiple sclerosis. Since macrophages appear to carry the major detectable antigen burden in vivo, and purification of sufficient cell num bers from the CNS for detailed analysis is difficult, macrophagelike cell l ines provide an accessible system with which to study virus-macrophage inte ractions. The myeloid precursor cell line M1 differentiates in response to cytokines and expresses many characteristics of tissue macrophages. Incubat ion of TMEV with undifferentiated M1 cells produced neither infection nor a poptosis, whereas differentiated M1 (M1-D) cells developed a restricted vir us infection and changes indicative of apoptosis. Virus binding and RNA rep lication as well as cellular production of alpha/beta interferons increased with differentiation. Although the amount of infectious virus was highly r estricted, BeAn-infected M1-D cells synthesized and appropriately processed virus capsid proteins at levels comparable to those for permissive BHK-21 cells. Analysis of Bcl-2 protein family expression in undifferentiated and differentiated cells suggests that susceptibility of M1-D cells to apoptosi s may be controlled, in part, by expression of the proapoptotic alpha isofo rm of Bax and Bak. These data suggest that macrophage differentiation plays a role in susceptibility to TMEV infection and apoptosis.