The Human Metapneumovirus Matrix Protein Stimulates the Inflammatory Immune Response In Vitro

Bagnaud-Baule, Audrey; Reynard, Olivier; Perret, Magali; Berland, Jean-Luc; Maache, Mimoun; Peyrefitte, Christophe N.; Vernet, Guy; Volchkov, Viktor E.; Paranhos-Baccalà, Gláucia

doi:10.1371/journal.pone.0017818

Cited by 14 publications

(13 citation statements)

References 43 publications

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“…These differences are probably the result of distinct pattern recognition receptors engaged by infectious and inactivated virus in DCs, such as Toll-like receptors, retinoic acid-inducible gene-1-like family receptors and protein kinase R. For instance, some Toll-like receptors may engage virion molecules present both in infectious and inactivated viruses, such as the hMPV matrix protein. 40 On the other hand, molecules such as protein kinase R, Toll-like receptor 3, and retinoic acid-inducible gene-1-like family receptors are specialized at recognizing RNA species that mainly occur in replicating viruses. [41][42][43] However, despite the recognition of viable or inactivated virus (UV-treated), we observed that DCs secreted poor amounts of cytokines that support T-cell activation, such as IL-12 and TNF-a.…”

Section: Discussionmentioning

confidence: 99%

Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

2013

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SummaryHuman metapneumovirus (hMPV) is the second most common cause of acute lower respiratory tract infections in children, causing a significant public health burden worldwide. Given that hMPV can repeatedly infect the host without major antigenic changes, it has been suggested that hMPV may have evolved molecular mechanisms to impair host adaptive immunity and, more specifically, T-cell memory. Recent studies have shown that hMPV can interfere with superantigen-induced T-cell activation by infecting conventional dendritic cells (DCs). Here, we show that hMPV infects mouse DCs in a restricted manner and induces moderate maturation. Nonetheless, hMPV-infected DCs are rendered inefficient at activating naive antigen-specific CD4 + T cells (OT-II), which not only display reduced proliferation, but also show a marked reduction in surface activation markers and interleukin-2 secretion. Decreased T-cell activation was not mediated by interference with DC-T-cell immunological synapse formation as recently described for the human respiratory syncytial virus (hRSV), but rather by soluble factors secreted by hMPV-infected DCs. These data suggest that although hMPV infection is restricted within DCs, it is sufficient to interfere with their capacity to activate naive T cells. Altogether, by interfering with DC function and productive priming of antigen-inexperienced T cells, hMPV could impair the generation of long-term immunity.

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Section: Discussionmentioning

confidence: 99%

Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

2013

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“…157 The M protein, which participates in virus assembly and packaging, 158 stimulates the inflammatory response in vitro by inducing the maturation of monocyte-derived DCs and the secretion of inflammatory cytokines by these cells, including IL-8, IL-6, IL-1b and TNF-a ( Table 2). 159 In addition, the M2-1 protein is critical for hMPV replication and pathogenesis through its Zinc binding activity, since a recombinant hMPV carrying mutations in the zinc binging motif was highly attenuated in cotton rats. 160 This is consistent with studies that demonstrate that hMPV lacking the M2-1 gene could not replicate in hamsters.…”

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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“…The significance of the spherical M protein staining pattern is unclear, but does suggest that in addition to the virus particle associated M protein, a second population of the M protein that does not show a similar staining to that observed using either anti-G or anti-F staining. This alternative M protein staining pattern may be related to the cell-free form of the M protein that has been described in HMPV-infected cells [ 22 ]. In addition, our previous studies employing recombinant expression to generate HMPV virus like particles (VLPs) [ 23 ] identified a population of the HMPV M protein that was secreted within membrane vesicles but which did not co-purify with the VLPs [ 23 ].…”

Section: Resultsmentioning

confidence: 99%

Imaging analysis of human metapneumovirus-infected cells provides evidence for the involvement of F-actin and the raft-lipid microdomains in virus morphogenesis

Jumat

Huong

Wong

et al. 2014

Virol J

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BackgoundDue to difficulties of culturing Human metapneumovirus (HMPV) much of the current understanding of HMPV replication can be inferred from other closely related viruses. The slow rates of virus replication prevent many biochemical analyses of HMPV particles. In this study imaging was used to examine the process of HMPV morphogenesis in individually infected LLC-MK2 cells, and to better characterise the sites of HMPV assembly. This strategy has circumvented the problems associated with slow replication rates and allowed us to characterise both the HMPV particles and the sites of HMPV morphogenesis.MethodsHMPV-infected LLC-MK2 cells were stained with antibodies that recognised the HMPV fusion protein (F protein), attachment protein (G protein) and matrix protein (M protein), and fluorescent probes that detect GM1 within lipid-raft membranes (CTX-B-AF488) and F-actin (Phalloidin-FITC). The stained cells were examined by confocal microscopy, which allowed imaging of F-actin, GM1 and virus particles in HMPV-infected cells. Cells co-expressing recombinant HMPV G and F proteins formed virus-like particles and were co-stained with antibodies that recognise the recombinant G and F proteins and phalloidin-FITC and CTX-B-AF594, and the distribution of the G and F proteins, GM1 and F-actin determined.ResultsHMPV-infected cells stained with anti-F, anti-G or anti-M revealed a filamentous staining pattern, indicating that the HMPV particles have a filamentous morphology. Staining of HMPV-infected cells with anti-G and either phalloidin-FITC or CTX-B-AF488 exhibited extensive co-localisation of these cellular probes within the HMPV filaments. This suggested that lipid-raft membrane domains and F-actin structures are present at the site of the virus morphogenesis, and are subsequently incorporated into the HMPV filaments. Furthermore, the filamentous virus-like particles that form in cells expressing the G protein formed in cellular structures containing GM1 and F-actin, suggesting the G protein contains intrinsic targeting signals to the sites of virus assembly.ConclusionsThese data suggest that HMPV matures as filamentous particles and that virus morphogenesis occurs within lipid-raft microdomains containing localized concentrations of F-actin. The similarity between HMPV morphogenesis and the closely related human respiratory syncytial virus suggests that involvement of F-actin and lipid-raft microdomains in virus morphogenesis may be a common feature of the Pneumovirinae.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-014-0198-8) contains supplementary material, which is available to authorized users.

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The Human Metapneumovirus Matrix Protein Stimulates the Inflammatory Immune Response In Vitro

Cited by 14 publications

References 43 publications

Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

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

Imaging analysis of human metapneumovirus-infected cells provides evidence for the involvement of F-actin and the raft-lipid microdomains in virus morphogenesis

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