Human Metapneumovirus M2-2 Protein Inhibits Innate Cellular Signaling by Targeting MAVS

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

doi:10.1128/jvi.01248-12

Cited by 49 publications

(113 citation statements)

References 56 publications

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“…161 However, is not essential for hMPV infectivity and growth in vitro as deletion of the ORF of the M2-1 protein is dispensable for viral replication in VERO cells. 161 In contrast, the hMPV M2-2 protein, defined as a terminator factor, since it inhibits viral replication and transcription, 162 interact with MAVS, 163 a protein that links the cytoplasmic viral sensors RIG-I and the melanoma differentiation associated protein 5 (MDA5) to the downstream TNF receptor-associated factors (TRAFs) and IkB kinases (IKKs), which are known to induce the type I IFN-pathway through the activation of IRF-3 and NFkB. 163 Thus, hMPV M2-2 protein contributes in decreasing efficiently the anti-viral response.…”

Section: Hmpv Molecular Characteristics and The Role Of Its Viral Promentioning

confidence: 99%

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

et al. 2016

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Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity. The modulation of immune response exerted by both viruses include different strategies such as, impairment of immunological synapse mediated by viral proteins or soluble factors, and the induction of pro-inflammatory cytokines by epithelial cells, among others. All these viral strategies contribute to the alteration of the adaptive immunity in order to increase the susceptibility to reinfections.In this review, we discuss current research related to the mechanisms underlying the impairment of T and B cell immune responses induced by hRSV and hMPV infection. In addition, we described the role each virulence factor involved in immune modulation caused by these viruses.

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Section: Hmpv Molecular Characteristics and The Role Of Its Viral Promentioning

confidence: 99%

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

et al. 2016

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“…Identifying viral proteins which are important for antiviral signalling regulation is also critical in vaccine design. Recently, we identified that some viral proteins, such as G and M2-2, play significant roles in suppressing hMPVinduced host innate immunity (Bao et al, 2008b(Bao et al, , 2013Kolli et al, 2011;Ren et al, 2012). For M2-2 protein, we and others found that it is a protein with multiple functions.…”

Section: Sliligittlmentioning

confidence: 96%

“…Recombinant live attenuated viruses are generated from the cells transfected with the hMPV cDNA genome, with or without gene modification or deletion, with plasmids encoding individual proteins essential for forming the RdPp complex (Bao et al, 2008b;Biacchesi et al, 2004a;Ren et al, 2012). The attenuation of recombinant hMPV has been achieved by the deletion of certain accessory genes.…”

Section: Live Attenuated Vaccinesmentioning

confidence: 99%

“…For M2-2 protein, we and others found that it is a protein with multiple functions. It not only regulates viral gene transcription and viral RNA replication Ren et al, 2012), but also contains a CTL epitope and targets central adaptors for retinoic acid-inducible gene I (RIG-I) and Toll-like receptors (TLRs) (Herd et al, 2006;Kitagawa et al, 2010;Ren et al, 2012Ren et al, , 2014. In addition, M2-2 also plays a significant role in regulating the expression of miRNAs, some of which are important for the expression of immune related genes (Deng et al, 2014).…”

Section: Sliligittlmentioning

confidence: 99%

“…Whether hMPV M2-2 is a key regulatory factor involved in the switch of the viral RNA polymerase from viral gene transcription to viral genome replication, as with the RSV M2-2 protein, is still controversial Kitagawa et al, 2010;Ren et al, 2012). The phosphoprotein P, glycoprotein G, small hydrophobic protein SH and M2-2 protein have all been shown to modulate host immune responses (Bao et al, 2008a, b;Goutagny et al, 2010;Ren et al, 2012Ren et al, , 2014. Recombinant hMPVs, lacking G, SH and M-2, individually or in combination, or having P replaced with avian P, are attenuated Pham et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Recent vaccine development for human metapneumovirus

Ren

Phan

Bao

2015

Journal of General Virology

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Human metapneumovirus (hMPV) and respiratory syncytial virus, its close family member, are two major causes of lower respiratory tract infection in the paediatric population. hMPV is also a common cause of worldwide morbidity and mortality in immunocompromised patients and older adults. Repeated infections occur often, demonstrating a heavy medical burden. However, there is currently no hMPV-specific prevention treatment. This review focuses on the current literature on hMPV vaccine development. We believe that a better understanding of the role(s) of viral proteins in host responses might lead to efficient prophylactic vaccine development.

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

Choi

Chen

et al. 2020

Journal of Medical Virology

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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.

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Human Metapneumovirus M2-2 Protein Inhibits Innate Cellular Signaling by Targeting MAVS

Cited by 49 publications

References 56 publications

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

Recent vaccine development for human metapneumovirus

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

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