Susceptibility of peritoneal macrophages to infection by Theiler's virus.

Theiler's murine encephalomyelitis virus (TMEV) strains fall into two groups: high-neurovirulence GDVII virus results in rapidly fatal encephalitis, while low-neurovirulence BeAn and DA viruses produce persistent central nervous system (CNS) infection and inflammatory demyelinating disease. Because macrophages (Mphis) are key components in BeAn virus-induced demyelinating disease, we examined the susceptibility of primary peritoneal macrophages (pMphis) to BeAn infection in vitro. Freshly isolated, thioglycollate-elicited pMphis were resistant to BeAn virus infection even at high multiplicity of infection. In contrast, after incubation of thioglycollate-elicited pMphis at 37 degrees C for 4 days before infection, approximately half of the cells expressed virus antigen(s) and contained nicked DNA indicative of apoptosis. However, BeAn virus RNA replication and virus yields were highly restricted. Interestingly, about one-third of the cells were apoptotic but negative for virus RNA and antigen(s). Tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha) were elevated in BeAn-infected pMphi cultures suggesting that bystander killing may be responsible for the apoptosis seen in BeAn virus antigen-negative cells. These data show for the first time that pMphis are susceptible to BeAn virus infection, although the infection is highly restricted and most of these cells undergo BeAn-induced apoptosis.