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Smits S.L.,Viroclinics Biosciences | Smits S.L.,Erasmus Medical Center | van Hellemond J.J.,Erasmus Medical Center | Schapendonk C.M.E.,Erasmus Medical Center | And 5 more authors.
Emerging Infectious Diseases | Year: 2013

To identify unknown human viruses, we analyzed serum and cerebrospinal fluid samples from patients with unexplained paraplegia from Malawi by using viral metagenomics. A novel cyclovirus species was identified and subsequently found in 15% and 10% of serum and cerebrospinal fluid samples, respectively. These data expand our knowledge of cyclovirus diversity and tropism.


Reusken C.B.E.M.,National Health Research Institute | Haagmans B.L.,Erasmus Medical Center | Muller M.A.,University of Bonn | Gutierrez C.,University of Las Palmas de Gran Canaria | And 25 more authors.
The Lancet Infectious Diseases | Year: 2013

Background: A new betacoronavirus-Middle East respiratory syndrome coronavirus (MERS-CoV)-has been identified in patients with severe acute respiratory infection. Although related viruses infect bats, molecular clock analyses have been unable to identify direct ancestors of MERS-CoV. Anecdotal exposure histories suggest that patients had been in contact with dromedary camels or goats. We investigated possible animal reservoirs of MERS-CoV by assessing specific serum antibodies in livestock. Methods: We took sera from animals in the Middle East (Oman) and from elsewhere (Spain, Netherlands, Chile). Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. Results were confirmed by virus neutralisation tests for MERS-CoV and bovine coronavirus. Findings: 50 of 50 (100%) sera from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specific antibodies against MERS-CoV spike. Sera from European sheep, goats, cattle, and other camelids had no such antibodies. MERS-CoV neutralising antibody titres varied between 1/320 and 1/2560 for the Omani camel sera and between 1/20 and 1/320 for the Spanish camel sera. There was no evidence for cross-neutralisation by bovine coronavirus antibodies. Interpretation: MERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection. Funding: European Union, European Centre For Disease Prevention and Control, Deutsche Forschungsgemeinschaft. © 2013 Elsevier Ltd.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.3.3-9 | Award Amount: 15.97M | Year: 2009

The EMPERIE (European Management Platform for Emerging and Re-emerging Infectious disease Entities) consortium has its roots in the lessons learned by the majority of the participating centres during the recent SARS and HPAI H5N1 outbreaks. The mission of EMPERIE is to contribute to effectively countering the potential public health threat caused by new and emerging infectious diseases in Europe by establishing a powerful network capable of structural and systematic prediction, identification, modelling and surveillance of infectious diseases health threats and pathogens. In pursuit of this mission EMPERIE will establish a network of centres of excellence combining the expertise, techniques and resources necessary for effectively countering (re)-emerging infectious diseases. We will establish common processes, procedures and communication channels in the network linked to relevant stakeholder organisations and local grass root sites to contribute to a structural and systematic prediction, identification, modelling and surveillance of (re-)emerging infectious disease health threats and pathogens. Our focus will be new zoonotic viruses that may cause epidemics and viruses already present but yet unrecognised- in humans. Within this focus, we will attain proof of principle of the functioning of the network and the techniques, systems, procedures and resources in the following RNA viruses: Flaviviruses (e.g. Dengue, West-Nile virus), Alphaviruses (e.g. Chikungunya), Orthomyxoviruses (e.g. Influenza), Paramyxoviruses (e.g Henipah,) Coronaviruses, Bunyaviruses ( e.g. hantavirus) and Filoviruses


Smits S.L.,Viroclinics Biosciences
Emerging infectious diseases | Year: 2013

To identify unknown human viruses, we analyzed serum and cerebrospinal fluid samples from patients with unexplained paraplegia from Malawi by using viral metagenomics. A novel cyclovirus species was identified and subsequently found in 15% and 10% of serum and cerebrospinal fluid samples, respectively. These data expand our knowledge of cyclovirus diversity and tropism.


Hillaire M.L.B.,Erasmus Medical Center | Haagsman H.P.,University Utrecht | Osterhaus A.D.M.E.,Erasmus Medical Center | Osterhaus A.D.M.E.,Viroclinics Biosciences | And 3 more authors.
Journal of Innate Immunity | Year: 2013

Influenza A viruses (IAV) cause respiratory tract infections annually associated with excess mortality and morbidity. Nonspecific, innate immune mechanisms play a key role in protection against viral invasion at early stages of infection. A soluble protein present in mucosal secretions of the lung, surfactant protein D (SP-D), is an important component of this initial barrier that helps to prevent and limit IAV infections of the respiratory epithelium. This collagenous C-type lectin binds IAVs and thereby inhibits attachment and entry of the virus but also contributes to enhanced clearance of SP-D-opsonized virus via interactions with phagocytic cells. In addition, SP-D modulates the inflammatory response and helps to maintain a balance between effective neutralization/killing of IAV, and protection against alveolar damage resulting from IAV-induced excessive inflammatory responses. The mechanisms of interaction between SP-D and IAV not only depend on the structure and binding properties of SP-D but also on strain-specific features of IAV, and both issues will be discussed. SP-D from pigs exhibits distinct anti-IAV properties and is discussed in more detail. Finally, the potential of SP-D as a prophylactic and/or therapeutic antiviral agent to protect humans against infections by IAV is discussed. Copyright © 2013 S. Karger AG, Basel.


Hillaire M.L.B.,Erasmus Medical Center | Osterhaus A.D.M.E.,Erasmus Medical Center | Osterhaus A.D.M.E.,Viroclinics Biosciences | Rimmelzwaan G.F.,Erasmus Medical Center | Rimmelzwaan G.F.,Viroclinics Biosciences
Journal of Biomedicine and Biotechnology | Year: 2011

There is considerable interest in the development of broadly protective influenza vaccines because of the continuous emergence of antigenic drift variants of seasonal influenza viruses and the threat posed by the emergence of antigenically distinct pandemic influenza viruses. It has been recognized more than three decades ago that influenza A virus-specific cytotoxic T lymphocytes recognize epitopes located in the relatively conserved proteins like the nucleoprotein and that they cross-react with various subtypes of influenza A viruses. This implies that these CD8 + T lymphocytes may contribute to protective heterosubtypic immunity induced by antecedent influenza A virus infections. In the present paper, we review the evidence for the role of virus-specific CD8 + T lymphocytes in protective immunity against influenza virus infections and discuss vaccination strategies that aim at the induction of cross-reactive virus-specific T-cell responses. Copyright © 2011 Marine L. B. Hillaire et al.


van den Brand J.M.A.,Erasmus Medical Center | Stittelaar K.J.,Viroclinics Biosciences | van Amerongen G.,Erasmus Medical Center | Reperant L.,Erasmus Medical Center | And 4 more authors.
PLoS ONE | Year: 2012

Humans may be infected by different influenza A viruses-seasonal, pandemic, and zoonotic-which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues-including the central nervous system-for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets. © 2012 van den Brand et al.


Bodewes R.,Erasmus Medical Center | Kreijtz J.H.C.M.,Erasmus Medical Center | Van Amerongen G.,Erasmus Medical Center | Fouchier R.A.M.,Erasmus Medical Center | And 5 more authors.
American Journal of Pathology | Year: 2011

Most patients infected with highly pathogenic avian influenza A/H5N1 virus develop severe pneumonia resulting in acute respiratory distress syndrome, with extrarespiratory disease as an uncommon complication. Intranasal inoculation of ferrets with influenza A/H5N1 virus causes lesions in both the respiratory tract and extrarespiratory organs (primarily brain). However, the route of spread to extrarespiratory organs and the relative contribution of extrarespiratory disease to pathogenicity are largely unknown. In the present study, we characterized lesions in the respiratory tract and central nervous system (CNS) of ferrets (n = 8) inoculated intranasally with influenza virus A/Indonesia/5/2005 (H5N1). By 7 days after inoculation, only 3 of 8 ferrets had a mild or moderate bronchointerstitial pneumonia. In contrast, all 8 ferrets had moderate or severe CNS lesions, characterized by meningoencephalitis, choroiditis, and ependymitis, and centered on tissues adjoining the cerebrospinal fluid. These findings indicate that influenza A/H5N1 virus spread directly from nasal cavity to brain, and that CNS lesions contributed more than pulmonary lesions to the pathogenicity of influenza A/H5N1 virus infection in ferrets. In comparison, intratracheal inoculation of ferrets with the same virus reproducibly caused severe bronchointerstitial pneumonia. The method of virus inoculation requires careful consideration in the design of ferret experiments as a model for influenza A/H5N1 in humans. © 2011 American Society for Investigative Pathology.


The amount of the deal was not disclosed. Founded in 2001 as a spin-off from the virology department at the Erasmus Medical Centre in Rotterdam, the Netherlands, and led by Bob van Gemen, CEO, Viroclinics Biosciences BV is a virology contract research organization, serving the biopharmaceutical community as a pre-clinical and clinical reference laboratory for supporting the development of new chemical entities, vaccines and antiviral compounds targeting viral infectious diseases. At the start of 2013, it opened a samples processing facility in Boston USA. With the transaction, the founding institute Erasmus University Medical Center (Erasmus MC) exited the company. Viroclinics intends now to use the proceeds to expand service its offering and plans to continue its collaboration with the Viroscience lab of Erasmus MC and co-develop new laboratory services in the field of virology.

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