Expression of the Sendai (murine parainfluenza) virus C protein alleviates restriction of measles virus growth in mouse cells
- 13 September 2011
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (37), 15384-15389
- https://doi.org/10.1073/pnas.1107382108
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.Keywords
This publication has 49 references indexed in Scilit:
- A genetically humanized mouse model for hepatitis C virus infectionNature, 2011
- The Matrix Protein of Measles Virus Regulates Viral RNA Synthesis and Assembly by Interacting with the Nucleocapsid ProteinJournal of Virology, 2009
- Measles Virus Circumvents the Host Interferon Response by Different Actions of the C and V ProteinsJournal of Virology, 2008
- A Human Lung Carcinoma Cell Line Supports Efficient Measles Virus Growth and Syncytium Formation via a SLAM- and CD46-Independent MechanismJournal of Virology, 2007
- Importance of the Anti-Interferon Capacity of Sendai Virus C Protein for Pathogenicity in MiceJournal of Virology, 2007
- Measles Virus Infection of SLAM (CD150) Knockin Mice Reproduces Tropism and Immunosuppression in Human InfectionJournal of Virology, 2007
- Translational Inhibition and Increased Interferon Induction in Cells Infected with C Protein-Deficient Measles VirusJournal of Virology, 2006
- High Pathogenicity of Wild-Type Measles Virus Infection in CD150 (SLAM) Transgenic MiceJournal of Virology, 2006
- Measles Virus Infects and Suppresses Proliferation of T Lymphocytes from Transgenic Mice Bearing Human Signaling Lymphocytic Activation MoleculeJournal of Virology, 2003
- Measles Virus Infection in a Transgenic Model: Virus-Induced Immunosuppression and Central Nervous System DiseaseCell, 1999