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

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

Research output: Contribution to journalArticle

28 Citations (Scopus)

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

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Human metapneumovirus
Metapneumovirus
cell communication
Proteins
Viral Genes
proteins
transcription (genetics)
immune evasion
Immune Evasion
Reverse Genetics
genes
viral proteins
live vaccines
Viral Proteins
Virulence Factors
Virus Diseases
G-proteins
Reporter Genes
GTP-Binding Proteins
respiratory system

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Human metapneumovirus M2-2 protein inhibits innate cellular signaling by targeting MAVS. / Ren, Junping; Wang, Qingrong; Kolli, Deepthi; Prusak, Deborah J.; Tseng, Chien-Te; Chen, Zhijian J.; Li, Kui; Wood, Thomas; Bao, Xiaoyong.

In: Journal of Virology, Vol. 86, No. 23, 12.2012, p. 13049-13061.

Research output: Contribution to journalArticle

Ren, J, Wang, Q, Kolli, D, Prusak, DJ, Tseng, C-T, Chen, ZJ, Li, K, Wood, T & Bao, X 2012, 'Human metapneumovirus M2-2 protein inhibits innate cellular signaling by targeting MAVS', Journal of Virology, vol. 86, no. 23, pp. 13049-13061. https://doi.org/10.1128/JVI.01248-12
Ren, Junping ; Wang, Qingrong ; Kolli, Deepthi ; Prusak, Deborah J. ; Tseng, Chien-Te ; Chen, Zhijian J. ; Li, Kui ; Wood, Thomas ; Bao, Xiaoyong. / Human metapneumovirus M2-2 protein inhibits innate cellular signaling by targeting MAVS. In: Journal of Virology. 2012 ; Vol. 86, No. 23. pp. 13049-13061.
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