Human metapneumovirus M2-2 protein inhibits innate cellular signaling by targeting MAVS

Junping Ren, Qingrong Wang, Deepthi Kolli, Deborah J. Prusak, Chien Te K Tseng, Zhijian J. Chen, Kui Li, Thomas G. Wood, Xiaoyong Bao

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Human metapneumovirus (hMPV) is a leading cause of respiratory infections in pediatric populations globally, with no prophylactic or therapeutic measures. Recently, a recombinant hMPV lacking the M2-2 protein (rhMPV-ΔM2-2) demonstrated reduced replication in the respiratory tract of animal models, making it a promising live vaccine candidate. However, the exact nature of the interaction between the M2-2 protein and host cells that regulates viral infection/propagation is largely unknown. By taking advantage of the available reverse genetics system and ectopic expression system for viral protein, we found that M2-2 not only promotes viral gene transcription and replication but subverts host innate immunity, therefore identifying M2-2 as a novel virulence factor, in addition to the previously described hMPV G protein. Since we have shown that the RIG-I/MAVS pathway plays an important role in hMPV-induced signaling in airway epithelial cells, we investigated whether M2-2 antagonizes the host cellular responses by targeting this pathway. Reporter gene assays and coimmunoprecipitation studies indicated that M2-2 targets MAVS, an inhibitory mechanism different from what we previously reported for hMPV G, which affects RIG-I- but not MAVSdependent gene transcription. In addition, we found that the domains of M2-2 responsible for the regulation of viral gene transcription and antiviral signaling are different. Our findings collectively demonstrate that M2-2 contributes to hMPV immune evasion through the inhibition of MAVS-dependent cellular responses.

Original languageEnglish (US)
Pages (from-to)13049-13061
Number of pages13
JournalJournal of virology
Volume86
Issue number23
DOIs
StatePublished - Dec 2012

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Ren, J., Wang, Q., Kolli, D., Prusak, D. J., Tseng, C. T. K., Chen, Z. J., Li, K., Wood, T. G., & Bao, X. (2012). Human metapneumovirus M2-2 protein inhibits innate cellular signaling by targeting MAVS. Journal of virology, 86(23), 13049-13061. https://doi.org/10.1128/JVI.01248-12