Claude P Muller

Luxembourg Institute of Health, Letzeburg, Luxembourg, Luxembourg

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Publications (192)733.26 Total impact

  • 45th ISPNE Annual Conference, Edinburgh; 08/2015
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    ABSTRACT: Cuba is an HBsAg low-prevalence country with a high coverage of anti-hepatitis B vaccine. Its population is essentially the result of the population mix of Spanish descendants and former African slaves. Information about genetic characteristics of hepatitis B virus (HBV) strains circulating in the country is scarce. The HBV genotypes/subgenotypes, serotypes, mixed infections, and S gene mutations of 172 Cuban HBsAg and HBV-DNA positive patients were determined by direct sequencing and phylogenetic analysis. Phylogenetic analysis of HBV S gene sequences showed a predominance of genotype A (92.4%), subgenotype A2 (84.9%) and A1 (7.6%). Genotype D (7.0%) and subgenotype C1 (0.6%) were also detected but typical (sub)genotypes of contemporary West-Africa (E, A3) were conspicuously absent. All genotype A, D, and C strains exhibited sequence characteristics of the adw2, ayw2, and adrq serotypes, respectively. Thirty-three (19.1%) patients showed single, double, or multiple point mutations inside the Major Hydrophilic domain associated with vaccine escape; eighteen (10.5%) patients had mutations in the T-cell epitope (amino acids 28-51), and there were another 111 point mutations downstream of the S gene. One patient had an HBV A1/A2 mixed infection. This first genetic study of Cuban HBV viruses revealed only strains that were interspersed with strains from particularly Europe, America, and Asia. The absence of genotype E supports previous hypotheses about an only recent introduction of this genotype into the general population in Africa. The presence of well-known vaccine escape (3.5%) and viral resistance mutants (2.9%) warrants strain surveillance to guide vaccination and treatment strategies.
    PLoS ONE 05/2015; 10(5-5):e0125052. DOI:10.1371/journal.pone.0125052 · 3.23 Impact Factor
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    ABSTRACT: Background: During late 2012 and early 2013 several outbreaks of diphtheria were notified in the North of the Lao People's Democratic Republic. The aim of this study was to determine whether the re-emergence of this vaccine-preventable disease was due to insufficient vaccination coverage or reduction of vaccine effectiveness within the affected regions. Methods: A serosurvey was conducted in the Huaphan Province on a cluster sampling of 132 children aged 12-59 months. Serum samples, socio-demographic data, nutritional status and vaccination history were collected when available. Anti-diphtheria and anti-tetanus IgG antibody levels were measured by ELISA. Results: Overall, 63.6% of participants had detectable diphtheria antibodies and 71.2% tetanus antibodies. Factors independently associated with non-vaccination against diphtheria were the distance from the health centre (OR: 6.35 [95% CI: 1.4-28.8], p = 0.01), the Lao Theung ethnicity (OR: 12.2 [95% CI:1,74-85, 4], p = 0.01) and the lack of advice on vaccination given at birth (OR: 9.8 [95% CI: 1.5-63.8], (p = 0.01) while the level of maternal edu-cation was a protective factor (OR: 0.08 [95% CI: 0.008-0.81], p = 0.03). Most respondents claimed financial difficulties as the main reason for non-vaccination. Out of 55 children whose vaccination certificates stated that they were given all 3 doses of diphtheria-containing vaccine, 83.6% had diphtheria antibodies and 92.7% had tetanus antibodies. Furthermore, despite a high prevalence of stunted and underweight children (53% and 25.8%, respectively), the low levels of anti-diphtheria antibodies were not correlated to the nutritional status. Conclusions: Our data highlight a significant deficit in both the vaccination coverage and diphtheria vaccine effectiveness within the Huaphan Province. Technical deficiencies in the methods of storage and distribution of vaccines as well as unreliability of vaccination cards are discussed. Several hypotheses are advanced to explain such a decline in immunity against diphtheria and recommendations are provided to prevent future outbreaks.
    PLoS ONE 04/2015; 10(4):e0121749. DOI:10.1371/journal.pone.0121749 · 3.23 Impact Factor
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    ABSTRACT: Background and aims: Healthcare workers (HCW) have an increased risk of exposure to infectious diseases and are a potential source of infections for their patients. The Lao People's Democratic Republic (Lao PDR) has no national policy regarding HCW vaccinations and routine vaccination coverage is low within the general population. This cross-sectional serostudy determines the level of exposure and risk of infection in Lao HCW against 6 vaccine preventable diseases and hepatitis C. Methods: 1128 HCW were recruited from 3 central, 2 provincial and 8 district hospitals. Sera were tested by ELISA for the presence of antibodies and antigens to hepatitis B, hepatitis C, measles, rubella, varicella zoster, tetanus and diphtheria. Results: Only 53.1% of the HCW had protective anti-hepatitis B surface antigen antibodies (anti-HBs) with 48.8% having anti-hepatitis B core antibodies (anti-HBc), indicating previous exposure and 8.0% were hepatitis B surface antigen carriers. 3.9% were hepatitis C seropositive. Measles and rubella antibodies were detected in 95.4% and 86.2% of the HCW, with 11.9% of females being unprotected against rubella. Antibodies against varicella zoster, tetanus and diphtheria were detected in 95%, 78.8% and 55.3%, respectively. Seroprevalence varied according to age, gender and number of children. Conclusion: An unacceptably high proportion of Lao HCW remain susceptible to infection with hepatitis B, diphtheria, tetanus and rubella. Furthermore, a high number of healthcare workers are chronically infected with hepatitis B and C viruses. These data emphasize the need for a robust HCW vaccination policy in addition to increased awareness within this subpopulation.
    PLoS ONE 04/2015; 10(4):e0123647. DOI:10.1371/journal.pone.0123647 · 3.23 Impact Factor
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    ABSTRACT: An increasing number of asthma cases upon exposure to hamsters and anaphylactic reactions following hamster bites are being reported, but the allergens responsible are still poorly characterized. In the Golden hamster, male-specific submaxillary gland protein (MSP), a lipocalin expressed in a sex- and tissue-specific manner in the submaxillary and lacrimal glands, is secreted in the saliva, tears and urine. The purpose of this study was to determine if MSP is an allergen, to identify IgE-reactive proteins of different hamster species and to analyse potential cross-reactivities. Fur extracts were prepared from four hamster species. Hamster-allergic patients were selected based on a history of positive IgE-test to hamster epithelium. The IgE-reactivity of patients' sera was investigated by means of immunoblot and ELISA. IgE-reactive proteins in fur extracts and the submaxillary gland were identified using anti-MSP antibodies, Edman sequencing or mass spectrometry. MSP was purified from Golden hamster and recombinant MSP was expressed in E. coli. Four patients had IgE-antibodies against 20.5-kDa and 24-kDa proteins of Golden hamster fur extract, which were identified as MSP. IgE-reactive MSP-like proteins were detected in European hamster fur extract. Three patient sera showed IgE-reactive bands at 17-21 kDa in Siberian and Roborovski hamster fur extracts. These proteins were identified as two closely related lipocalins. Immunoblot inhibition experiments showed that they are cross-reactive and are different from MSP. MSP lipocalin of the Golden hamster was identified as an allergen, and it is different from the cross-reactive lipocalin allergens of Siberian and Roborovski hamsters. Our findings highlight the need for specific tools for the in vitro and in vivo diagnosis of allergy to different hamster species. © 2015 S. Karger AG, Basel.
    International Archives of Allergy and Immunology 02/2015; 166(1):30-40. DOI:10.1159/000371420 · 2.67 Impact Factor
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    ABSTRACT: The worst Ebola virus (EV) outbreak in history has hit Liberia, Sierra Leone and Guinea hardest and the trendlines in this crisis are grave, and now represents global public health threat concern. Limited therapeutic and/or prophylactic options which are available for humans suffering from Ebola virus disease (EVD) further complicate situation. Previous studies suggested that the EV glycoprotein (GP) is the main determinant causing structural damage of endothelial cells that triggers the hemorrhagic diathesis, but molecular mechanisms underlying this phenomenon remains elusive. Using the informational spectrum method (ISM), a virtual spectroscopy method for analysis of the protein-protein interactions, the interaction of GP with endothelial extracellular matrix (ECM) was investigated. Presented results of this in silico study suggest that Elastin Microfibril Interface Located Proteins (EMILINs) are involved in interaction between GP and ECM. This finding could contribute to better understanding of EV/endothelium interaction and its role in pathogenesis, prevention and therapy of EVD.
    Frontiers in Microbiology 02/2015; 6:135. DOI:10.3389/fmicb.2015.00135 · 3.99 Impact Factor
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    ABSTRACT: Background and Objective: Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. Material and Methods: Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. Results: Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1β in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone. Conclusion: Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis.
    The Open Dentistry Journal 01/2015; DOI:10.2174/1874210601509010065
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    ABSTRACT: Besides birds, pigs are another important reservoir of influenza A viruses that can be transmitted to human, as highlighted by the emergence and spread of the pandemic (H1N1) virus (pdm/09) in 2009. Surveillance in pigs is therefore necessary for public health and influenza pandemic preparedness. Nevertheless, there is a serious lack of data on influenza in Africa, especially in swine. We therefore collected serum samples from pigs in Nigeria (2009, 2012) and Cameroon (2011) in which the presence of anti-influenza A neutralizing antibodies was investigated. Our serological survey suggests that, before the 2009 pandemic, only rare swine and human H3N2 or human H1N1 infections occurred in Nigeria in swine. However, in 2011-2012, 27.4% of pigs in Nigeria and 5,6% in Cameroon had antibodies against H1N1 viruses. Higher antibody titers against pdm/09 suggested that pigs were exposed to this or a similar virus, either by multiple introductions or sustained circulation, and that reactivity against American and European swine H1N1 viruses resulted from cross-reaction.
    Veterinary Microbiology 01/2015; 176(1-2). DOI:10.1016/j.vetmic.2014.12.022 · 2.51 Impact Factor
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    ABSTRACT: The external environment plays a primordial role in determining gene expression, and protein production, which may in turn define a behavioral or physiological phenotype. This control occurs at both the transcriptional and translational levels and involves a wide range of mechanisms, providing a plethora of opportunities for altering the final level of functional proteins. These mechanisms all share the common feature that they do not alter the underlying genomic sequence, but they act as biological annotations to the genome. In this section we review these mechanisms, and how they are related to health. In particular the role of the three epigenetic mechanisms in controlling the glucocorticoid receptor, as well as the stress phenotype, are reviewed in detail.
    International Encyclopedia of Social and Behavioural Sciences, 2nd Edition edited by Jame D Wright, 12/2014; Elsevier.
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    ABSTRACT: Despite hepatitis B vaccination at birth and at 6, 10 and 14 weeks of age, hepatitis B virus (HBV) infection continues to be endemic in the Lao People’s Democratic Republic (PDR). We carried out a cross-sectional serological study in infants, pre-school children, school pupils and pregnant women to determine their burden of disease, risk of infection and vaccination status. A total of 2471 participants between 9 months and 46 years old were recruited from urban (Vientiane Capital, Luang Prabang), semi-urban (Boulhikhamxai and Savannakhet) and remote rural areas (Huaphan). All sera were tested for anti-HBs and anti-HBc. Sera testing positive for anti-HBc alone were further tested for the presence of HBsAg. A low prevalence of HBsAg (0.5%) was detected among infants from Vientiane and Luang Prabang, indicating some success of the vaccination policy. However, only 65.6% had protective anti-HBs antibodies, suggesting that vaccination coverage or responses remain sub-optimal, even in these urban populations. In pre-school children from remote areas in Huaphan, 21.2% were positive for anti-HBc antibodies, and 4.6% were for HBsAg positive, showing that a significant proportion of children in these rural regions have early exposure to HBV. In pre-school children with 3 documented HBV vaccinations, only 17.0% (15/55) were serologically protected. Among school-children from semi-urban regions of Luang Prabang, Boulhikhamxai and Savannakhet provinces, those below the age of 9 who were born after HBV vaccine introduction had anti-HBc and HBsAg prevalence of 11.7% and 4.1%, respectively. The prevalence increased to 19.4% and 7.8% of 10–14 year olds and to 27% and 10.2% of 15–19 year olds. Pregnant women from Luang Prabang and Vientiane had very high anti-HBc and HBsAg prevalence (49.5% and 8.2%), indicating high exposure and risk of onward vertical transmission to the unborn infant. Overall, the results demonstrate a dramatic deficiency in vaccination coverage and vaccine responses and/or documentation within the regions of Lao PDR studied, which included urbanized areas with better health care access. Timely and effective hepatitis B vaccination coverage is needed in Lao PDR.
    BMC Infectious Diseases 08/2014; 14(1):457. DOI:10.1186/1471-2334-14-457 · 2.61 Impact Factor
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    ABSTRACT: GR transcripts display a remarkable heterogeneity in their 5' untranslated regions (5'UTRs). These variable 5'UTRs are encoded by a series of alternative 1st exons, and together with their associated promoters they maintain tissue-specific GR expression levels. In this study we over-expressed GR transcripts containing individual 1st exons, and assessed their effect on RNA stability, 3'-splicing, translation initiation and protein isoform production. We showed that these alternative 5'UTRs influence the predicted mRNA structure and free energy, and were associated with differential levels of functional spliced mRNA. However, the 5'UTR had little influence on the relative levels of the two principal 3' splice transcripts, GR-α and -β. The overall mRNA length, the free energy of the transcript and the translational efficiency directly influenced total GR levels. However, individual N-terminal protein isoform levels appeared to depend upon elements within the 5'UTR. Membrane-GR specific labelling suggested that the mGR originates from transcripts containing exon 1D and possibly 1H, although the specific trafficking sequences or structures within these transcripts remain unidentified. The role of the alternative first exons and their associated 5'UTRs has now been expanded to translational control, influencing total GR levels, individual constituent isoform levels, as well as trafficking to the cell surface.
    Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 08/2014; 1839(11). DOI:10.1016/j.bbagrm.2014.08.010 · 6.33 Impact Factor
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    ABSTRACT: Unlabelled: Quantitative gel-based proteomics (2D DIGE coupled to MALDI-TOF/TOF MS) has been used to investigate the effects of different measles virus (MV) strains on the host cell proteome. A549/hSLAM cells were infected either with wild type MV strains, an attenuated vaccine or a multiple passaged Vero cell adapted strain. By including interferon beta treatment as a control it was possible to distinguish between the classical antiviral response and changes induced specifically by the different strains. Of 38 differentially expressed proteins in total (p-value ≤0.05, fold change ≥2), 18 proteins were uniquely modulated following MV infection with up to 9 proteins specific per individual strain. Interestingly, wt strains displayed distinct protein patterns particularly during the late phase of infection. Proteins were grouped into cytoskeleton, metabolism, transcription/translation, immune response and mitochondrial proteins. Bioinformatics analysis revealed mostly changes in proteins regulating cell death and apoptosis. Surprisingly, wt strains affected the cytokeratin system much stronger than the vaccine strain. To our knowledge, this is the first study on the MV-host proteome addressing interstrain differences. Biological significance: In the present study we investigated the host cell proteome upon measles virus (MV) infection. The novelty about this study is the side-by side comparison of different strains from the same virus, which has not been done at the proteome level for any other virus including MV. We used different virus strains including a vaccine strain, wild type isolates derived from MV-infected patients as well as a Vero cell adapted strain, which serves as an intermediate between vaccine and wild type strain. We observed differences between vaccine and wild type strains as well as common features between different wild type strains. Perhaps one of the most surprising findings was that differences did not only occur between wild type and vaccine or Vero cell adapted strains but also between different wild type strains. In fact our study suggests that besides the cytokeratin and the IFN system wild type viruses seem to differ as much among each other than from vaccine strains. Thus our results are suggestive of complex and diverse virus-host interactions which differ considerably between different wild type strains. Our data indicate that interstrain differences are prominent and have so far been neglected by proteomics studies.
    Journal of Proteomics 06/2014; 108. DOI:10.1016/j.jprot.2014.05.029 · 3.89 Impact Factor
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    Omer Adam · Ahmed Km Ali · Judith M Hübschen · Claude P Muller
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    ABSTRACT: Background Epidemiological data about congenital rubella syndrome (CRS) are scarce and rubella vaccine is not yet included in the childhood immunization schedule in Sudan. This study aimed to identify and describe CRS cases among Sudanese infants with congenital eye or heart defects. Methods Between February and September 2010, paired oral fluid and dried blood spot samples were collected from 98 infants aged up to 12 months. These infants were enrolled during their visits to five hospitals in Khartoum, Sudan. Clinical samples were screened for rubella IgM and for ≥ 6 months old infants also for IgG antibodies by ELISA. The oral fluid of IgM and/or IgG positive patients was tested for rubella RNA by reverse transcriptase PCR. Results Our findings revealed that two children (2.0%) were IgM positive and another five children (5.1%) were positive for IgG antibodies. None of the five infants of which enough oral fluid was available for RNA investigation was PCR positive. Conclusions This study documented the presence of CRS in Sudan and highlighted the importance of rubella vaccine introduction for preventing future CRS cases in the country.
    BMC Infectious Diseases 06/2014; 14(1):305. DOI:10.1186/1471-2334-14-305 · 2.61 Impact Factor
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    ABSTRACT: The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that Akt inhibitor MK2206, blocks influenza pH1N1 virus infection in vitro. In particular, at non-cytotoxic concentrations MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9 and H5N1 viruses indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus.
    Antimicrobial Agents and Chemotherapy 04/2014; 58(7). DOI:10.1128/AAC.02798-13 · 4.48 Impact Factor
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    ABSTRACT: Several viruses, amongst others human papillomaviruses, depend on endosomal acidification for successful infection. Hence, the multi-subunit enzyme vacuolar ATPase, which is mainly responsible for endosome acidification in the cell, represents an attractive target for antiviral strategies. In the present study we show that V-ATPase is required for human papillomavirus (HPV) infection and that uncoating/disassembly, but not endocytosis, is affected by V-ATPase inhibition. The infection inhibitory potency of Saliphenylhalamide, a proven V-ATPase inhibitor, its derivatives and other V-ATPase inhibitors was analyzed on different HPV types in relevant cell lines. Variation in the selectivity index among V-ATPase inhibitors was high while variation for the same inhibitor against different HPV subtypes was low indicating that broad-spectrum anti-HPV activity can be provided.
    Antimicrobial Agents and Chemotherapy 03/2014; 58(5). DOI:10.1128/AAC.02284-13 · 4.48 Impact Factor
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    ABSTRACT: Hepatitis D virus (HDV) is a satellite virus of hepatitis B virus (HBV) infection that aggravates acute and chronic liver disease. While HBV seroprevalence is very high across sub-Saharan Africa, much less is known about HDV in the region. In this study almost 2300 serum samples from Burkina Faso (n=1131), Nigeria (n=974), Chad (n=50) and the Central African Republic (n=118) were screened for HBV and HDV. Among 743 HBsAg positive sera 74 were positive for HDV-antibodies and/or HDV-RNA, with considerable differences in prevalence, ranging from <2% (pregnant women from Burkina Faso) to 50% (liver patients from Central African Republic). HDV seems to be a lot more frequent in chronic liver disease patients in CAR than in the similar cohorts in Nigeria. In a large nested mother-child cohort in Burkina Faso the prevalence of HDV antibodies was ten times higher in the children than in the mother, despite similar HBsAg prevalences, excluding vertical transmission as an important route of infection.
    Journal of clinical microbiology 03/2014; 52(5). DOI:10.1128/JCM.02297-13 · 3.99 Impact Factor
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    ABSTRACT: In Lao People's Democratic Republic (PDR), mumps is not a notifiable disease and mumps vaccine is currently not included in the routine childhood immunization program. In order to assess the burden of disease, we investigated the seroprevalence of mumps-specific IgG antibodies across four provinces. In addition, we genetically characterized mumps viruses from the past 3 years from several outbreaks and single cases. Blood and/or throat swabs from suspected cases were investigated for specific IgM antibodies or viral RNA. Mumps cases occurred between March and November in 2011-2013 and 5-15 year olds were most affected. Four sequences from an outbreak in the North of Lao PDR in 2011 were identical and belonged to genotype G. Eight sequences from two outbreaks and two individual cases from 2012 and 2013 belonged to genotype J. In addition, sera collected from 2379 healthy infants and school pupils between 9 months and 19 years and from pregnant women between 16 and 46 years were investigated for mumps-specific IgG. Overall, 58.2% were positive, 39.5% were negative and the remaining 2.3% were equivocal. The seropositivity increased with age, with the lowest percentage found in the <1 year old infants (9.1%) and the highest in the cohort of pregnant women (69.2%). More females than males were seropositive (60.4 versus 54.9%). There were some differences between the locations. Mumps should be a notifiable disease in Lao PDR to get more accurate case numbers and cost estimates for public health and vaccination of children and high-risk groups should be considered. This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 02/2014; 20(10). DOI:10.1111/1469-0691.12586 · 5.77 Impact Factor
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    ABSTRACT: Although there is currently no evidence of emerging strains of measles virus (MV) that can resist neutralization by the anti-MV antibodies present in vaccinees, certain mutations in circulating wt MV strains appear to reduce the efficacy of these antibodies. Moreover, it has been hypothesized that resistance to neutralization by such antibodies could allow MV to persist. In this study, we use a novel in vitro system to determine the molecular basis of MV’s resistance to neutralization. We find that both wild-type and laboratory strain MV variants that escape neutralization by anti-MV polyclonal sera possess multiple mutations in their H, F, and M proteins. Cytometric analysis of cells expressing viral escape mutants possessing minimal mutations and their plasmid-expressed H, F, and M proteins indicates that immune resistance is due to particular mutations that can occur in any of these three proteins that affect at distance, rather than directly, the native conformation of the MV-H globular head and hence its epitopes. A high percentage of the escape mutants contain mutations found in cases of Subacute Sclerosing Panencephalitis (SSPE) and our results could potentially shed light on the pathogenesis of this rare fatal disease.
    Advances in Virology 02/2014; 2014(2):205617. DOI:10.1155/2014/205617
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    ABSTRACT: Antiviral activity has been demonstrated for different tannin-rich plant extracts. Since tannins of different classes and molecular weights are often found together in plant extracts and may differ in their antiviral activity, we have compared the effect against influenza A virus (IAV) of Hamamelis virginiana L. bark extract, fractions enriched in tannins of different molecular weights and individual tannins of defined structures, including pseudotannins. We demonstrate antiviral activity of the bark extract against different IAV strains, including the recently emerged H7N9, and show for the first time that a tannin-rich extract inhibits human papillomavirus (HPV) type 16 infection. As the best performing antiviral candidate, we identified a highly potent fraction against both IAV and HPV, enriched in high molecular weight condensed tannins by ultrafiltration, a simple, reproducible and easily upscalable method. This ultrafiltration concentrate and the bark extract inhibited early and, to a minor extent, later steps in the IAV life cycle and tannin-dependently inhibited HPV attachment. We observed interesting mechanistic differences between tannin structures: High molecular weight tannin containing extracts and tannic acid (1702 g/mol) inhibited both IAV receptor binding and neuraminidase activity. In contrast, low molecular weight compounds (<500 g/mol) such as gallic acid, epigallocatechin gallate or hamamelitannin inhibited neuraminidase but not hemagglutination. Average molecular weight of the compounds seemed to positively correlate with receptor binding (but not neuraminidase) inhibition. In general, neuraminidase inhibition seemed to contribute little to the antiviral activity. Importantly, antiviral use of the ultrafiltration fraction enriched in high molecular weight condensed tannins and, to a lesser extent, the unfractionated bark extract was preferable over individual isolated compounds. These results are of interest for developing and improving plant-based antivirals.
    PLoS ONE 01/2014; 9(1):e88062. DOI:10.1371/journal.pone.0088062 · 3.23 Impact Factor
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    ABSTRACT: GR transcripts display a remarkable heterogeneity in their 5’ untranslated regions (5’UTRs). These variable 5’UTRs are encoded by a series of alternative 1st exons, and together with their associated promoters they maintain tissue-specific GR expression levels. In this study we over-expressed GR transcripts containing individual 1st exons, and assessed their effect on RNA stability, 3’-splicing, translation initiation and protein isoform production. We showed that these alternative 5’UTRs influence the predicted mRNA structure and free energy, and were associated with differential levels of functional spliced mRNA. However, the 5’UTR had little influence on the relative levels of the two principal 3’ splice transcripts, GR-α and -β. The overall mRNA length, the free energy of the transcript and the translational efficiency directly influenced total GR levels. However, individual N-terminal protein isoform levels appeared to depend upon elements within the 5’UTR. Membrane-GR specific labelling suggested that the mGR originates from transcripts containing exon 1D and possibly 1H, although the specific trafficking sequences or structures within these transcripts remains unidentified. The role of the alternative first exons and their associated 5’UTRs has now been expanded to translational control, influencing total GR levels, individual constituent isoform levels, as well as trafficking to the cell surface.
    Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 01/2014; · 6.33 Impact Factor

Publication Stats

3k Citations
733.26 Total Impact Points


  • 2015
    • Luxembourg Institute of Health
      Letzeburg, Luxembourg, Luxembourg
  • 2014
    • National Institute of Public Health, Lao PDR Equitap
      Viangchan, Vientiane, Laos
  • 2011–2014
    • LIH Luxembourg Institute of Health
      • Department of Immunology
      Letzeburg, Luxembourg, Luxembourg
    • National Centre of Infectious and Parasitic Diseases, Bulgaria
      Ulpia Serdica, Sofia-Capital, Bulgaria
  • 2005–2014
    • Universität Trier
      • Institute of Psychobiology
      Trier, Rheinland-Pfalz, Germany
    • Catholic University of Louvain
      Лувен-ла-Нев, Walloon, Belgium
  • 2013
    • University of Lorraine
      Nancy, Lorraine, France
  • 2000–2012
    • University of Ibadan
      • Department of Chemical Pathology & Immunology
      Ibadan, Oyo, Nigeria
  • 1996–2012
    • Laboratoire National de Santé
      Letzeburg, Luxembourg, Luxembourg
  • 2010
    • Centers for Disease Control and Prevention
      Atlanta, Michigan, United States
  • 2009
    • Gezond Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2007
    • University of Luxembourg
      Letzeburg, Luxembourg, Luxembourg
    • Institut Pasteur de Tunis
      Tunis-Ville, Tūnis, Tunisia
  • 2006
    • University of Lagos
      Eko, Lagos, Nigeria
  • 1999
    • Université Libre de Bruxelles
      Bruxelles, Brussels Capital Region, Belgium
  • 1998
    • University of Tuebingen
      • Faculty of Medicine
      Tübingen, Baden-Württemberg, Germany
  • 1997
    • University of Lausanne
      • Department of Biochemistry
      Lausanne, VD, Switzerland