Evasion of host defenses by measles virus: Wild-type measles virus infection interferes with induction of alpha/beta interferon production

Measles is a highly contagious disease currently responsible for over one m illion childhood deaths, particularly in the developing world. Since alpha/ beta interferons (IFNs) are pivotal players both in nonspecific antiviral i mmunity and in specific cellular responses, their induction or suppression by measles virus (MV) could influence the outcome of a viral infection. In this study we compare the IFN induction and sensitivity of laboratory-passa ged attenuated MV strains Edmonston and Moraten with those of recent wild-t ype viruses isolated and passaged solely on human peripheral blood mononucl ear cells (PBMC) or on the B958 marmoset B-cell line. We report that two PB MC-grown wild-type measles isolates and two B958-grown strains of MV induce 10- to 10-fold-lower production of IFN by phytohemagglutinin-stimulated pe ripheral blood lymphocytes (PBL) compared to Edmonston and Moraten strains of measles. Preinfection of PBL with these non-IFN-inducing MV isolates pre vents Edmonston-induced but not double-stranded-RNA-induced IFN production. This suggests that the wild-type viruses can actively inhibit Edmonston-in duced IFN synthesis and that this is not occurring by double-stranded RNA. Furthermore, the wild-type MV is more sensitive than Edmonston MV to the ef fect of IFN, MV is thus able to suppress the synthesis of the earliest medi ator of antiviral immunity, IFN-alpha/beta. This could have important impli cations in the virulence and spread of MV.