Computational prediction of intracellular targets of wild-type or mutant vesicular stomatitis matrix protein
Department
Research
Document Type
Article
Publication Title
PloS One
Abstract
The matrix (M) protein of vesicular stomatitis virus (VSV) has a complex role in infection and immune evasion, particularly with respect to suppression of Type I interferon (IFN). Viral strains bearing the wild-type (wt) M protein are able to suppress Type I IFN responses. We recently reported that the 22-25 strain of VSV encodes a wt M protein, however its sister plaque isolate, strain 22-20, carries a M[MD52G] mutation that perturbs the ability of the M protein to block NFκB, but not M-mediated inhibition of host transcription. Therefore, although NFκB is activated in 22-20 infected murine L929 cells infected, no IFN mRNA or protein is produced. To investigate the impact of the M[D52G] mutation on immune evasion by VSV, we used transcriptomic data from L929 cells infected with wt, 22-25, or 22-20 to define parameters in a family of executable logical models with the aim of discovering direct targets of viruses encoding a wt or mutant M protein. After several generations of pruning or fixing hypothetical regulatory interactions, we identified specific predicted targets of each strain. We predict that wt and 22-25 VSV both have direct inhibitory actions on key elements of the NFκB signaling pathway, while 22-20 fails to inhibit this pathway.
First Page
e0263065
DOI
10.1371/journal.pone.0263065
Volume
17
Issue
2
Publication Date
2-2-2022
PubMed ID
35108303
Recommended Citation
Morris, M. C., Russell, T. M., Lyman, C. A., Wong, W. K., Broderick, G., & Ferran, M. C. (2022). Computational prediction of intracellular targets of wild-type or mutant vesicular stomatitis matrix protein. PloS One, 17 (2), e0263065. https://doi.org/10.1371/journal.pone.0263065