Proteomic Analysis Uncovers Measles Virus Protein C Interaction With p65-iASPP Protein Complex

Viruses manipulate the central machineries of host cells to their advantage. They prevent host cell antiviral responses to create a favorable environment for their survival and propagation. Measles virus (MV) encodes two nonstructural proteins MV-V and MV-C known to counteract the host interferon response and to regulate cell death pathways. Several molecular mechanisms underlining MV-V regulation of innate immunity and cell death pathways have been proposed, whereas MV-C host-interacting proteins are less studied. We suggest that some cellular factors that are controlled by MV-C protein during viral replication could be components of innate immunity and the cell death pathways. To determine which host factors are targeted by MV-C, we captured both direct and indirect host-interacting proteins of MV-C protein. For this, we used a strategy based on recombinant viruses expressing tagged viral proteins followed by affinity purification and a bottom-up mass spectrometry analysis. From the list of host proteins specifically interacting with MV-C protein in different cell lines, we selected the host targets that belong to immunity and cell death pathways for further validation. Direct protein interaction partners of MV-C were determined by applying protein complementation assay and the bioluminescence resonance energy transfer approach. As a result, we found that MV-C protein specifically interacts with p65–iASPP protein complex that controls both cell death and innate immunity pathways and evaluated the significance of these host factors on virus replication.
Graphical Abstract
Highlights • Measles virus controls immune response and cell death pathways to achieve replication. • Host proteins interaction network with measles virulence factor C protein. • Cellular p65–iASPP complex is targeted by measles virus C protein.
In Brief Control of measles virus infection and measles-based oncolytic therapy are possible, thanks to the existence of a safe and efficient live attenuated vaccine. Molecular mechanisms that make this vaccine to be so efficient are yet to be determined. We show that the measles C protein is responsible for the establishment of complex networks of interactions with the host cell. We suggest that the C protein binding to the p65–iASPP protein complex controls the host cell death and innate immunity pathways.