Interplay of measles virus with early induced cytokines reveals different wild type phenotypes

Differential effects of measles virus (MV) on the innate immune response may influence virus spread and severity of disease. Using a representative panel of 22 MV strains including 14 different genotypes, we found that wild-type (wt) differ considerably in their sensitivity to type I interferon (IFN). The wt virus production was 2-47-fold lower in IFN-alpha treated Vero/hSLAM cells, whereas vaccine virus production was reduced only 2-3-fold. Sequence analysis of the MV-P/C/V gene, revealed no obvious amino acid mutations that correlated with the different phenotypes. Strains also widely differed in their ability to induce type I IFN, tumor necrosis factor (TNF) alpha and other cytokines in human A549/hSLAM cells. Some wt strains that were highly sensitive to type I IFN induced only low levels of these and other cytokines. In vitro wt strains that produced the 5' copy-back defective interfering RNAs (5'cb-diRNA) characterized by Shingai et al. (2007), induced high levels of cytokines that otherwise were only reached by vaccine strains. These 5'cb-diRNAs emerged only in virus cultures during multiple passaging and were not detectable in clinical samples of measles patients. These subgenomic RNAs are an important confounding parameter in passaged wt viruses which must be carefully assessed in all in vitro studies. The present data show that MV wt strains differ in their sensitivity and their ability to temper with the innate immune response, which may result in differences in virulence.