Manuel Rosa-Calatrava

University of Lyon, Lyons, Rhône-Alpes, France

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Publications (40)159.42 Total impact

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    ABSTRACT: Air quality on aircraft cabins has become a major public health issue due to the increasing number of air travels since few decades. Exposure to Volatile Organic Compounds (VOC) and micro-organisms is a major concern for human and animal welfare in indoor confinements and especially in aircraft cabins. Here we present an innovative air purification system based on the association of UV-C and photocatalysis. The SAVAB project is aiming at a higher decontamination degree of aircraft cabin air, thus improving health and comfort standards of aircraft crew and passengers. We show a reduction of irritating/noxious VOC such as formaldehyde, toluene, benzene, acetone, which are major pollutants of the aircraft cabins according the NF EN 4618 regulation. In the same study, we also demonstrate the inactivation of pathogenic Influenza virus, adenovirus and pathogenic bacteria such as Legionella pneumophila, Burkholderia cepacia, Streptococcus pneumoniae and Pseudomonas aeruginosa. This innovative system demonstrates its ability to improve air quality in indoor confinements of travel-motorised units such as aircraft cabins and could be applied in hospital environments.
    CLEAN - Soil Air Water 06/2014; 42(6):703–712. · 2.05 Impact Factor
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    ABSTRACT: In this study, we investigated the ultrastructural modifications induced by influenza A (H7N9) virus in human lung epithelial cells. One particular characteristic of H7N9 viral infection is the formation of numerous M1-associated striated tubular structures within the nucleus and the cytoplasm, which have only previously been observed for a limited number of influenza A viruses, notably the 2009 pandemic (H1N1) virus.
    Virology 05/2014; s 456–457:39–42. · 3.37 Impact Factor
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    Julia Dubois, Olivier Terrier, Manuel Rosa-Calatrava
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    ABSTRACT: During their nuclear replication stage, influenza viruses hijack the host splicing machinery to process some of their RNA segments, the M and NS segments. In this review, we provide an overview of the current knowledge gathered on this interplay between influenza viruses and the cellular spliceosome, with a particular focus on influenza A viruses (IAV). These viruses have developed accurate regulation mechanisms to reassign the host spliceosome to alter host cellular expression and enable an optimal expression of specific spliced viral products throughout infection. Moreover, IAV segments undergoing splicing display high levels of similarity with human consensus splice sites and their viral transcripts show noteworthy secondary structures. Sequence alignments and consensus analyses, along with recently published studies, suggest both conservation and evolution of viral splice site sequences and structure for improved adaptation to the host. Altogether, these results emphasize the ability of IAV to be well adapted to the host's splicing machinery, and further investigations may contribute to a better understanding of splicing regulation with regard to viral replication, host range, and pathogenesis.
    mBio 01/2014; 5(3). · 6.88 Impact Factor
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    ABSTRACT: Influenza A viruses cause annual influenza epidemics and occasional severe pandemics. Their genome is segmented into eight fragments, which offers evolutionary advantages but complicates genomic packaging. The existence of a selective packaging mechanism, in which one copy of each viral RNA is specifically packaged into each virion, is suspected, but its molecular details remain unknown. Here, we identified a direct intermolecular interaction between two viral genomic RNA segments of an avian influenza A virus using in vitro experiments. Using silent trans-complementary mutants, we then demonstrated that this interaction takes place in infected cells and is required for optimal viral replication. Disruption of this interaction did not affect the HA titer of the mutant viruses, suggesting that the same amount of viral particles was produced. However, it nonspecifically decreased the amount of viral RNA in the viral particles, resulting in an eightfold increase in empty viral particles. Competition experiments indicated that this interaction favored copackaging of the interacting viral RNA segments. The interaction we identified involves regions not previously designated as packaging signals and is not widely conserved among influenza A virus. Combined with previous studies, our experiments indicate that viral RNA segments can promote the selective packaging of the influenza A virus genome by forming a sequence-dependent supramolecular network of interactions. The lack of conservation of these interactions might limit genetic reassortment between divergent influenza A viruses.
    Proceedings of the National Academy of Sciences 09/2013; · 9.81 Impact Factor
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    ABSTRACT: The fragmented nature of the influenza A genome allows the exchange of gene segments when two or more influenza viruses infect the same cell, but little is known about the rules underlying this process. Here, we studied genetic reassortment between the A/Moscow/10/99 (H3N2, MO) virus originally isolated from human and the avian A/Finch/England/2051/91 (H5N2, EN) virus and found that this process is strongly biased. Importantly, the avian HA segment never entered the MO genetic background alone but always was accompanied by the avian PA and M fragments. Introduction of the 5' and 3' packaging sequences of HAMO into an otherwise HAEN backbone allowed efficient incorporation of the chimerical viral RNA (vRNA) into the MO genetic background. Furthermore, forcing the incorporation of the avian M segment or introducing five silent mutations into the human M segment was sufficient to drive coincorporation of the avian HA segment into the MO genetic background. These silent mutations also strongly affected the genotype of reassortant viruses. Taken together, our results indicate that packaging signals are crucial for genetic reassortment and that suboptimal compatibility between the vRNA packaging signals, which are detected only when vRNAs compete for packaging, limit this process.
    Proceedings of the National Academy of Sciences 09/2013; · 9.81 Impact Factor
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    ABSTRACT: The interplay between influenza A viruses (IAV) and p53 has only been reported in a limited number of studies, mainly focusing on the antiviral role of p53. We investigated the impact of IAV infection on p53 stability and transcriptional activity. Our results indicate that IAV-induced stabilization of p53 only partially correlates with modulation of p53 transcriptional activity measured during infection. Moreover, we show that the viral non-structural protein 1 (NS1) is able to inhibit p53 transcriptional activity, in a promoter-dependent manner. Based on these data, we propose that NS1 may contribute to p53-mediated cell fate decision during IAV infection. p53physically interacts with NS1 by anti bait coimmunoprecipitation (View interaction).
    FEBS letters 08/2013; · 3.54 Impact Factor
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    ABSTRACT: The heat-shock protein 27 (HSP27) is up-regulated in tumor cells and released in their microenvironment. Here, we show that extracellular HSP27 has a proangiogenic effect evidenced on chick chorioallantoic membrane. To explore this effect, we test the recombinant human protein (rhHSP27) at physiopathological doses (0.1-10 μg/ml) onto human microvascular endothelial cells (HMECs) grown as monolayers or spheroids. When added onto HMECs, rhHSP27 dose-dependently accelerates cell migration (with a peak at 5 μg/ml) and favors spheroid sprouting within 12-24 h. rhHSP27 increases VEGF gene transcription and promotes secretion of VEGF-activating VEGF receptor type 2. Increased VEGF transcription is related to NF-κB activation in 30 min. All of these effects are initiated by rhHSP27 interaction with Toll-like receptor 3 (TLR3). Such an interaction can be detected by immunoprecipitation but does not seem to be direct, as we failed to detect an interaction between rhHSP27 and monomeric TLR3 by SPR analysis. rhHSP27 is rapidly internalized with a pool of TLR3 to the endosomal compartment (within 15-30 min), which is required for NF-κB activation in a cytosolic Ca(2+)-dependent manner. The HSP27/TLR3 interaction induces NF-κB activation, leading to VEGF-mediated cell migration and angiogenesis. Such a pathway provides alternative targets for antiangiogenic cancer therapy.-Thuringer, D., Jego, G., Wettstein, G., Terrier, O., Cronier, L., Yousfi, N., Hébrard, S., Bouchot, A., Hazoumé, A., Joly, A.-L., Gleave, M., Rosa-Calatrava, M., Solary, E., and Garrido, C. Extracellular HSP27 mediates angiogenesis through Toll-like receptor 3.
    The FASEB Journal 06/2013; · 5.70 Impact Factor
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    ABSTRACT: Human parainfluenza viruses (hPIV) are pathogens responsible for upper and lower respiratory tract infections. We previously described clinical variant strains of hPIV-2 that display unusual large syncytial cytopathic effects. Their molecular characterization revealed a recurrent conserved specific amino acid substitution: A96T in the F2 subunit of the fusion glycoprotein F. The objective of this study was to investigate the contribution of this A96T substitution to the specific hyperfusogenic properties of the hPIV-2 variant strains. Based on a transient expression strategy, quantification of cell-cell fusion assays, and flow cytometry, we have shown that the A96T mutation strongly alters the fusogenic properties of F hPIV-2, highlighting this key residue in the F2 subunit and its possible role in fusion regulation. This work highlights the benefits of monitoring genetic and phenotypic changes of circulating strains to complete our understanding of Paramyxovirus fusion and related pathogenesis.
    Virus Genes 06/2013; · 1.84 Impact Factor
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    Olivier Terrier, Jean-Christophe Bourdon, Manuel Rosa-Calatrava
    PLoS Pathogens 04/2013; 9(4):e1003246. · 8.14 Impact Factor
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    ABSTRACT: While post-transcriptional regulation of gene expression by miRNAs have been shown to be involved in influenza virus replication cycle, only a few studies have further investigated this aspect in a human cellular model infected with human influenza viruses. In this study, we performed miRNA global profiling in human lung epithelial cells (A549) infected by two different subtypes of human influenza A viruses (H1N1 and H3N2). We identified a common miRNA signature in response to infection by the two different strains, highlighting a pool of five miRNAs commonly deregulated, which are known to be involved in the innate immune response or apoptosis. Among the five miRNA hits, the only up-regulated miRNA in response to influenza infection corresponded to miR-146a. Based on a previously published gene expression dataset, we extracted inversely correlated miR-146a target genes and determined their first-level interactants. This functional analysis revealed 8 distinct biological processes strongly associated with these interactants: TLR pathway, innate immune response, cytokine production and apoptosis. To better understand the biological significance of miR-146a up-regulation, using a reporter assay and a specific anti-miR-146a inhibitor, we confirmed that infection increases the endogenous miR-146a promoter activity and that inhibition of miR-146a significantly increased viral propagation. Altogether, our results suggest a functional role of miR-146a in the outcome of influenza infection, at the crossroads of several biological processes.
    Journal of General Virology 01/2013; · 3.13 Impact Factor
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    ABSTRACT: Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus-host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtype origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.
    Virology 07/2012; 432(1):204-18. · 3.35 Impact Factor
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    ABSTRACT: Previous studies have described the role of p53 isoforms, including p53β and Δ133p53α, in the modulation of the activity of full-length p53, which regulates cell fate. In the context of influenza virus infection, an interplay between influenza viruses and p53 has been described, with p53 being involved in the antiviral response. However, the role of physiological p53 isoforms has never been explored in this context. Here, we demonstrate that p53 isoforms play a role in influenza A virus infection by using silencing and transient expression strategies in human lung epithelial cells. In addition, with the help of a panel of different influenza viruses from different subtypes, we also show that infection differentially regulates the expressions of p53β and Δ133p53α. Altogether, our results highlight the role of p53 isoforms in the viral cycle of influenza A viruses, with p53β and Δ133p53α acting as regulators of viral production in a p53-dependent manner.
    Journal of Virology 05/2012; 86(16):8452-60. · 5.08 Impact Factor
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    ABSTRACT: There is no vaccine currently approved for paramyxovirus-induced respiratory diseases in humans, despite their major clinical importance. We review the development and evaluation of new vaccine strategies based on live-attenuated chimeric and recombinant vaccines against human respiratory syncytial virus, human metapneumovirus and human parainfluenza viruses types 1 to 3, which are significant causes of upper and lower tract respiratory diseases. Most promising strategies are based on virus attenuation through (i) mutations in key genes involved in replication; (ii) deletion of accessory genes; or (iii) the use of a corresponding animal viral vector, such as bovine parainfluenza type 3 and Sendai virus, as a background for the expression of a viral glycoprotein. Indeed, the fusion (F), or attachment (HN/H/G) glycoproteins are the most immunogenic antigens in paramyxoviruses. For each strategy, we will review the immunogenicity (increase in neutralising antibody titres) and the protection conferred by the most promising recombinant vectored vaccines and list ongoing clinical trials. We will conclude by discussing the most important challenges regarding the introduction of such vaccines into immunisation programmes. Copyright © 2012 John Wiley & Sons, Ltd.
    Reviews in Medical Virology 05/2012; · 7.62 Impact Factor
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    ABSTRACT: Oncolytic adenoviruses are promising anticancer agents. To study and optimize their tumor-killing potency, genuine tumor models are required. Here we describe the use of the chicken chorioallantoic membrane (CAM) tumor model in studies on oncolytic adenoviral vectors. Suspensions of human melanoma, colorectal carcinoma and glioblastoma multiforme cell lines were grafted on the CAM of embryonated chicken eggs. All cell lines tested formed 5-10 mm size tumors, which recapitulated hallmarks of corresponding human specimens. Furthermore, melanoma tumors were injected with adenoviral vector-carrying gene encoding the fusion protein of parainfluenza virus type 5. This led to the induction of cell fusion and syncytia formation in the infected cells. At 6 days post-injection, histological and immunohistochemical analyses of tumor sections confirmed adenovirus replication and syncytia formation. These results demonstrate that the CAM model allows rapid assessment of oncolytic viruses in three-dimensional tumors. Hence, this model constitutes an easy and affordable system for preclinical characterization of viral oncolytic agents that may precede the mandatory process of animal testing. Application of this model will help reducing the use of human xenografts in mice for preclinical evaluation of oncolytic viruses and other anticancer agents.
    Cancer gene therapy 01/2012; 19(1):58-68. · 3.13 Impact Factor
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    ABSTRACT: Netrin-1 displays proto-oncogenic activity in several cancers, which is thought to be due to the ability of this secreted cue to stimulate survival when bound to its receptors. We showed that in contrast to full-length, secreted netrin-1, some cancer cells produced a truncated intranuclear form of netrin-1 (ΔN-netrin-1) through an alternative internal promoter. Because of a nucleolar localization signal located in its carboxyl terminus, ΔN-netrin-1 was targeted to the nucleolus, where it interacted with nucleolar proteins, affected nucleolar ultrastructure, and interacted with the promoters of ribosomal genes. Moreover, ΔN-netrin-1 stimulated cell proliferation in vitro and tumor growth in vivo. Thus, some cancer cells produce not only a full-length, secreted form of netrin-1 that promotes cell survival but also a truncated netrin-1 that stimulates cell proliferation, potentially by enhancing ribosome biogenesis.
    Science Signaling 01/2012; 5(236):ra57. · 7.65 Impact Factor
  • F Feuillet, B Lina, M Rosa-Calatrava, G Boivin
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    ABSTRACT: Described for the first time in 2001, human metapneumovirus (hMPV) has become one of the main viral pathogens responsible for acute respiratory tract infections in children but also in the elderly and immuno-compromised patients. The pathogen most closely related to hMPV is human respiratory syncytial virus (hRSV), the most common cause of bronchiolitis and pneumonia in young children. hMPV has been classified into two main viral groups A and B and has a seasonal distribution in temperate countries with most cases occurring in winter and spring. Given the difficulties encountered in culturing hMPV in vitro, diagnosis is generally achieved using real-time polymerase chain reaction. Like other Paramyxoviridae, hMPV has a negative-sense single-stranded RNA genome that includes 8 genes coding for 9 different proteins. The genomic organization and functions of surface attachment and fusion glycoproteins are relatively similar to those of hRSV. Although many groups have studied the viral life cycle of hMPV, many questions remain unanswered concerning the exact roles of the viral proteins in the attachment, fusion and replication of hMPV. To date, there remains no approved modality to combat hMPV infections. The majority of treatments that have been tested on hMPV have already demonstrated activity against hRSV infections. Some innovative approaches based on RNA interference and on fusion inhibitors have shown efficacy in vitro and in animal studies and could be beneficial in treating human hMPV disease. Difficulties faced inducing a durable immune response represent the biggest challenge in the development of an effective hMPV vaccine. Several strategies, such as the use of live-attenuated viruses generated by reverse genetics or recombinant proteins, have been tested in animals with encouraging results.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 11/2011; 53(2):97-105. · 3.12 Impact Factor
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    ABSTRACT: Only facepiece respirators of FFP2 or FFP3 type by European standards (N95 by US standards) can provide effective protection against airborne viruses. However, these respirators are expensive and many third-world countries would be unable to afford them if a severe pandemic starts. The present study reports a chemical modification of the surface of low-cost non-woven cellulosic fiber filters by fixing poly(ethylenimine) (PEI) in order to give them an antiviral property. The virus filtration experiments were performed by spraying an aerial suspension of T4D bacteriophage virus of Escherichia coli B through the filter. The coating of the non-woven fiber by the antiviral entity was optimized. The best virus capture factor f (ratio of mother-solution virus content to downstream virus content) was obtained with 2 layers of Kimwipes® functionalized with a PEI solution (4.4% w/v) (f=3×105). When these 2 layers were placed inside a commercial medical mask in place of its cellulosic layer (Kolmi M24001 mask) (f=3.5×104), the f ratio reached 1.8×10, 7for 1h of filtration. This novel medical mask with additional antiviral properties represents a significant improvement over conventional medical masks. The system was also tested with respect to the respiratory low pathogenic A (H5N2) influenza virus. No virus was detected on the downstream side of the filters during the filtration. Moreover, the system captured alive the virus making possible applications to pre-concentration of airborne viruses for medical tests or research experiments.
    Chemical Engineering Journal 09/2011; 173(2):341-351. · 3.47 Impact Factor
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    ABSTRACT: Influenza is one of the most common infectious diseases in humans occurring as seasonal epidemic and sporadic pandemic outbreaks. The ongoing infections of humans with avian H5N1 influenza A viruses (IAV) and the past 2009 pandemic caused by the quadruple human/avian/swine reassortant (H1N1) virus highlights the permanent threat caused by these viruses. This review aims to describe the interaction between the virus and the host, with a particular focus on the role of proteases and HLA-G in the pathogenicity of influenza viruses.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 07/2011; 51(3):155-9. · 3.12 Impact Factor
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    ABSTRACT: Influenza viruses can modulate and hijack several cellular signalling pathways to efficiently support their replication. We recently investigated and compared the cellular gene expression profiles of human lung A549 cells infected by five different subtypes of human and avian influenza viruses (Josset et al. Plos One 2010). Using these transcriptomic data, we have focused our analysis on the modulation of the p53 pathway in response to influenza infection. Our results were supported by both RT-qPCR and western blot analyses and reveal multiple alterations of the p53 pathway during infection. A down-regulation of mRNA expression was observed for the main regulators of p53 protein stability during infection by the complete set of viruses tested, and a significant decrease in p53 mRNA expression was also observed in H5N1 infected cells. In addition, several p53 target genes were also down-regulated by these influenza viruses and the expression of their product reduced. Our data reveal that influenza viruses cause an overall down-regulation of the host p53 pathway and highlight this pathway and p53 protein itself as important viral targets in the altering of apoptotic processes and in cell-cycle regulation.
    Virology Journal 06/2011; 8:285. · 2.09 Impact Factor
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    ABSTRACT: Despite progress in our knowledge of the internal organisation of influenza virus particles, little is known about the determinants of their morphology and, more particularly, of the actual abundance of structural proteins at the virion level. To address these issues, we used cryo-EM to focus on viral (and host) factors that might account for observed differences in virion morphology and characteristics such as size, shape and glycoprotein (GP) spike density. Twelve recombinant viruses were characterised in terms of their morphology, neuraminidase activity and virus growth. The genomic composition was shown to be important in determining the GP spike density. In particular, polymerase gene segments and especially PB1/PB2 were shown to have a prominent influence in addition to that for HA in determining GP spike density, a feature consistent with a functional link between these virus components important for virus fitness.
    Virology 04/2011; 414(1):51-62. · 3.35 Impact Factor

Publication Stats

415 Citations
159.42 Total Impact Points

Institutions

  • 2009–2014
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 2008–2014
    • Claude Bernard University Lyon 1
      • Unité de virologie et pathologie humaine
      Villeurbanne, Rhône-Alpes, France
    • University Joseph Fourier - Grenoble 1
      Grenoble, Rhône-Alpes, France
  • 2011–2012
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 2010
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2001–2002
    • Transgene
      Illkirch, Alsace, France
    • Institut de Génétique et de Biologie Moléculaire et Cellulaire
      Strasburg, Alsace, France