The role of M2-2 PDZ-binding motifs in pulmonary innate immune responses to human metapneumovirus

Eun Jin Choi, Wenzhe Wu, Yu Chen, Weiyu Yan, Liqing Li, Atanu Choudhury, Xiaoyong Bao

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Human metapneumovirus (HMPV) is a leading cause of lower respiratory tract infection (LRTI) in pediatric and geriatric populations. We recently found that two PDZ-binding motifs of the M2-2 protein, 29-DEMI-32 and 39-KEALSDGI-46, play a significant role in mediating HMPV immune evasion in airway epithelial cells (AECs). However, their role in the overall pulmonary responses to HMPV infection has not been investigated. In this study, we found that two recombinant HMPVs (rHMPV) lacking the individual M2-2 PDZ-binding motif are attenuated in mouse lungs. Mice infected with mutants produce more cytokines/chemokines in bronchoalveolar lavage (BAL) fluid compared to mice infected with wild-type rHMPV. In addition, both mutants are able to enhance the pulmonary recruitment of dendritic cells (DCs) and T cells and induce effective protections against the HMPV challenge. The DC maturation is also significantly improved by the motif mutation. Taken together, our data provide proof-of-principle for two live-attenuated M2-2 mutants to be promising HMPV vaccine candidates that are effective in inducing higher pulmonary innate immunity and generating protection against HMPV infection.

Original languageEnglish (US)
JournalJournal of Medical Virology
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • HMPV
  • PDZ-binding motif
  • innate immunity
  • pulmonary innate response

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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