Expression of the Sendai (murine parainfluenza) virus C protein alleviates restriction of measles virus growth in mouse cells

Abstract

Measles virus (MV), a human pathogen, uses the signaling lymphocyte activation molecule (SLAM) or CD46 as an entry receptor. Although several transgenic mice expressing these receptors have been generated as small animal models for measles, these mice usually have to be made defective in IFN-α/β signaling to facilitate MV replication. Similarly, when functional receptors are expressed by transfection, mouse cells do not allow MV growth as efficiently as primate cells. In this study, we demonstrate that MV efficiently grows in SLAM-expressing mouse cells in which the Sendai virus (SeV) C protein is transiently expressed. We developed a SLAM-expressing mouse cell line whose genome also encodes the SeV C protein downstream of the sequence flanked with loxP sequences. When this cell line was infected with the recombinant MV expressing the Cre recombinase, the SeV C protein was readily expressed. Importantly, the Cre recombinase-encoding MV grew in this cell line much more efficiently than it did in the parental cell. The minigenome assay demonstrated that the SeV C protein does not modulate MV RNA synthesis. Analyses using the mutant proteins with the defined functional defects revealed that the IFN-antagonist function, but not the budding-accelerating function, of the SeV C protein was critical for supporting efficient MV growth in mouse cells. Our results indicate that insufficient IFN antagonism can be an important determinant of the host range of viruses, and the system described here may be useful to overcome the species barrier of other human viruses.

Paramyxovirus evasion of innate immunity: Diverse strategies for common targets

“…Importantly, IFN antagonism has been implicated as a key factor in host and tissue specificity, with PIV5 showing limited host range dependent on the capacity of the V protein to bind to STAT2 from different species [129][130][131][132] , whereas NiV V blocks IFN signalling in cells of many species, consistent with its broad infectious range [82,110,124,126] . Tissue-specific antagonism of IFN has also been reported for NiV, which induces an IFN response in endothelial but not neuronal cells, correlating with differential subcellular localisation of NiV W [133] .…”

Actin-Modulating Protein Cofilin Is Involved in the Formation of Measles Virus Ribonucleoprotein Complex at the Perinuclear Region

“…Vero/human SLAM (hSLAM) cells (3), HeLa/hSLAM cells (32), and HEK293/hSLAM cells (33), which stably express human SLAM, were maintained in Dulbecco modified Eagle medium (DMEM; Wako Pure Chemical Industries) supplemented with 10% fetal bovine serum and penicillin-streptomycin (Gibco). IC323 is a recombinant MV based on the pathogenic IC-B strain (34).…”

Characterization and Comparison of SLAM/CD150 in Free-Ranging Coyotes, Raccoons, and Skunks in Illinois for Elucidation of Canine Distemper Virus Disease

“…Additionally, such studies could also facilitate an assessment of SLAM/CD150 receptor upregulation with CDV infection providing insight into host immune response or mechanisms of viral cell-to-cell spread. Further investigation of intracellular pathways following viral binding is also warranted as the combination of receptors and downstream intracellular mechanics has been implicated as a contributing factor to the host range in measles virus infections [ 27 ]. It is interesting to note that coyote amino acid sequences in this study had 100% homology with domestic canine sequences, yet equivalent severe disease in coyotes is not the norm despite serologic evidence of consistent exposure and infection in the FPDCC population.…”