Human metapneumovirus M2-2 protein inhibits innate immune response in monocyte-derived dendritic cells

Junping Ren, Guangliang Liu, Jonathan Go, Deepthi Kolli, Guanping Zhang, Xiaoyong Bao

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Human metapneumovirus (hMPV) is a leading cause of lower respiratory infection in young children, the elderly and immunocompromised patients. Repeated hMPV infections occur throughout life. However, immune evasion mechanisms of hMPV infection are largely unknown. Recently, our group has demonstrated that hMPV M2-2 protein, an important virulence factor, contributes to immune evasion in airway epithelial cells by targeting the mitochondrial antiviral-signaling protein (MAVS). Whether M2-2 regulates the innate immunity in human dendritic cells (DC), an important family of immune cells controlling antigen presenting, is currently unknown. We found that human DC infected with a virus lacking M2-2 protein expression (rhMPV-DM2-2) produced higher levels of cytokines, chemokines and IFNs, compared to cells infected with wild-type virus (rhMPV-WT), suggesting that M2-2 protein inhibits innate immunity in human DC. In parallel, we found that myeloid differentiation primary response gene 88 (MyD88), an essential adaptor for Toll-like receptors (TLRs), plays a critical role in inducing immune response of human DC, as downregulation of MyD88 by siRNA blocked the induction of immune regulatory molecules by hMPV. Since M2-2 is a cytoplasmic protein, we investigated whether M2-2 interferes with MyD88-mediated antiviral signaling. We found that indeed M2-2 protein associated with MyD88 and inhibited MyD88-dependent gene transcription. In this study, we also identified the domains of M2-2 responsible for its immune inhibitory function in human DC. In summary, our results demonstrate that M2-2 contributes to hMPV immune evasion by inhibiting MyD88-dependent cellular responses in human DC.

Original languageEnglish (US)
Article numbere91865
JournalPLoS One
Volume9
Issue number3
DOIs
StatePublished - Mar 11 2014

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Human metapneumovirus
Metapneumovirus
dendritic cells
Innate Immunity
monocytes
Dendritic Cells
Monocytes
immune evasion
Immune Evasion
Proteins
proteins
Viruses
Antiviral Agents
Genes
infection
viruses
Toll-Like Receptors
Immunocompromised Host
Virulence Factors
Antigen-Presenting Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Human metapneumovirus M2-2 protein inhibits innate immune response in monocyte-derived dendritic cells. / Ren, Junping; Liu, Guangliang; Go, Jonathan; Kolli, Deepthi; Zhang, Guanping; Bao, Xiaoyong.

In: PLoS One, Vol. 9, No. 3, e91865, 11.03.2014.

Research output: Contribution to journalArticle

Ren, Junping ; Liu, Guangliang ; Go, Jonathan ; Kolli, Deepthi ; Zhang, Guanping ; Bao, Xiaoyong. / Human metapneumovirus M2-2 protein inhibits innate immune response in monocyte-derived dendritic cells. In: PLoS One. 2014 ; Vol. 9, No. 3.
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