Ron A M Fouchier

..These findings led us to propose that influenza virus infection in pigs might present different patterns, from an epidemic outbreak to an endemic form with different waves of infections with a lower incidence...

..Because H7N7 viruses have caused disease in mammals, including horses, seals, and humans, on several occasions in the past, they may be unusual in their zoonotic potential and, thus, form a pandemic threat to humans...

..Here, the authors review the current knowledge of the (molecular) epidemiology, genetics and evolution of LPAI viruses in wild birds, and identify some important gaps in current knowledge...

..Here we review the recent literature on these respiratory viruses...

..We propose that sequence analyses of HA and NA genes of influenza A viruses be used for the rapid identification of existing and novel HA and NA subtypes...

..Considerable antigenic variation was also observed within and between H5N1 clades. These observations have important implications for the efficacy and long-term use of poultry vaccines...

..Moreover, it will be important to discriminate this previously undescribed coronavirus from HCoV 229E and OC43 and the severe acute respiratory syndrome coronavirus...

..Here we provide a brief overview of some of the data from the past and give our view on how the continued and intensified animal influenza virus surveillance may aid in the early recognition and management of outbreaks in the future...

..Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza...

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..Further mapping of the molecular determinants of attenuation of HMPV should be the subject of future studies...

..Both vaccines induced HMPV-specific immune responses, but the rapid waning of immunity is a challenging obstacle for vaccine development...

..The data presented suggest that vaccine candidates based on low-pathogenicity avian influenza A viruses, which can be prepared ahead of pandemic threats, can be efficacious if an effective adjuvant is used...

..In contrast, two immunizations induced robust antibody responses and protected ferrets from developing severe disease, confirming that MVA is an attractive influenza vaccine production platform...

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..These data suggest that the 2009 A(H1N1) influenza virus has the ability to persist in the human population, potentially with more severe clinical consequences...

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..These data are useful for designing new surveillance programs and are particularly relevant due to increased interest in avian influenza in wild birds...

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..It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate...

..These findings may have implications for the general recommendation to vaccinate all healthy children against seasonal influenza in the light of the current pandemic threat caused by highly pathogenic avian A/H5N1 influenza viruses...

..These findings may have implications for vaccination strategies aimed at the induction of protective immunity to seasonal and/or pandemic influenza...

..These findings may explain, at least in part, the localization and severity of H5N1 viral pneumonia in humans. They also identify the cat and the ferret as suitable experimental animals based on this criterion...

..We conclude that the influenza virus HA and PB2 genes should be the prime targets for molecular surveillance during outbreaks of zoonotic HPAI viruses...

..The PVA in human respiratory tract most closely mirrored that in ferrets and pigs for human influenza viruses and that in ferrets, pigs, and cats for avian influenza viruses...

..In conclusion, a soluble F subunit vaccine for hMPV that induces cross-protective immunity for infection of the lower respiratory tract in Syrian golden hamsters has been generated...

..This study demonstrates that hMPV is a respiratory pathogen and indicates that viral replication is short-lived, polarized to the apical surface, and occurs primarily in ciliated respiratory epithelial cells...

..Altered receptor specificity of the virus with D222G thus affected interaction with cells of the human lower respiratory tract, possibly explaining the observed association with enhanced disease in humans...

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..In conclusion, HPAI H5N1 virus can spread systemically via two different routes, olfactory and hematogenous, in ferrets. This systemic spread was dependent on the presence of the MBCS in HA...

..Eight months later, protection had waned to virtually undetectable levels. This study demonstrates that experimental hMPV infection induces transient protective immunity...

..Three influenza pandemics of the previous century caused variable mortality, which largely depended on the development of severe pneumonia. However, the ability of the new H1N1 virus to cause pneumonia is poorly understood...

..It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted...

..This study indicates that acquisition of an MBCS alone is insufficient to increase pathogenicity of a prototypical seasonal human H3N2 virus...

..The method of virus inoculation requires careful consideration in the design of ferret experiments as a model for influenza A/H5N1 in humans...

..Virus attachment was not always predictive for efficient infection of the cells...

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..Thus, a reverse-genetics system for the rescue of Influenza A virus has been developed, which will be useful for fundamental research and vaccine seed strain production in a variety of cell lines...

..Our data suggest that recombinant MVA expressing the HA of influenza virus A/Vietnam/1194/04 is a promising alternative vaccine candidate that could be used for the induction of protective immunity against various H5N1 influenza strains...

..01). It was speculated that the high functional avidity of NP(418-426)-specific CTL was responsible for the diversification of this influenza A virus CTL epitope...

..Postexposure treatment with pegylated IFN-alpha yielded intermediate results. We therefore suggest that pegylated IFN-alpha protects type 1 pneumocytes from SCV infection, and should be considered a candidate drug for SARS therapy...

..The recombinant viruses replicated with kinetics similar to those of the parental viruses in Vero cells. This reverse genetics system provides an important new tool for applied and fundamental research...

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..These results suggest that the ability of an influenza virus to attach to human upper respiratory tract is a critical factor for efficient transmission in the human population...

..The relative genetic diversity observed in the four HMPV lineages was low, most likely reflecting continual population bottlenecks, with only limited evidence for positive selection...

..Moreover, the lessons learned from current large-scale influenza A virus surveillance activities could be valuable for other pathogen surveillance programs in the future...

..We did clinical and experimental studies to assess the role of this virus in the cause of SARS...

..This study provides insight into the determinants of host tropism and membrane fusion of metapneumoviruses...

..In contrast, the CTL response to influenza B virus was mainly directed toward HLA-B*0801-restricted epitopes. Thus, the preferential use of HLA alleles depended on the virus studied...

..The differences found between the evolution of NA and HA1 warrant further analysis of the evolution of NA at the phenotypic level, as has been done previously for HA...

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..This is particularly relevant if wild bird surveillance studies are used as an "early warning system" for the arrival of the H5N1 HPAI virus in a country or region and to assess the risk posed by these viruses in general...

..A mutational analysis of this epitope indicated that it is under functional constraints. Also in influenza A viruses of other subtypes, including H5N1, the M1(58-66) is highly conserved...

..Together, these results demonstrate the potential for heterogeneity in infection to have a profound influence on the dynamics of pathogens, with concomitant impacts on host habitat selection and fitness...

..It is important to be vigilant for this mutation in influenza surveillance and to continue efforts to increase the arsenal of antiviral drugs to combat influenza...

..This study in cats demonstrates that H5N1 virus infection causes systemic disease and spreads by potentially novel routes within and between mammalian hosts...

..It was speculated that influenza viruses could evade recognition by virus-specific CD4+ T-cells, at least temporarily...

..The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses, and screening of large sample collections from humans and animals...

..Treatment with antibiotics and corticosteroids was reported more frequently in hMPV-infected children. From these data, we conclude that hMPV is an important pathogen associated with RTI...

..The consequences of these findings are discussed in the light of the development of protective immunity to seasonal and future pandemic influenza viruses...

..Each serotype could be divided into two genetic lineages, but these did not reflect major antigenic differences...

..These PCR fragments can be sequenced directly without the need for cloning PCR fragments first. This method was used to sequence the NCRs of A/Bilthoven/16190/68 (H3N2) and A/Turkey/Turkey/1/05 (H5N1)...

..We conclude that sequences in the 5' and 3' ends of the polymerase gene segments contain packaging signals. Our methods will facilitate the further mapping of the packaging signals of influenza A virus...

..Only 6% of all HMPV lineage A F sequences have 294G, and none of the lineage B sequences have 294G. Thus, acidic pH is not a general trigger of HMPV F proteins for activity...

..The development of diagnostic assays must take into account the existence of two hMPV serotypes...

..Here we describe the development and evaluation of a real-time reverse transcriptase PCR assay that detects human metapneumovirus from the four known genetic lineages with equal specificities and sensitivities...

..In conclusion, high-titer virus stocks of recombinant influenza A/PR/8/34 virus can be produced as well as virus stocks with much lower titers, but without the requirement of virus amplification through replication...

..Various ideas and hypotheses about the roles of influenza virus RNA folding in the virus replication are also discussed in relation to other viruses...

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..In the present paper, the possibility to develop (cross-reactive) CTL-inducing vaccines is discussed...

..Here we give an overview of the immunogenicity and protective efficacy of a variety of live attenuated, virus vectored, inactivated virus and subunit vaccines that have been tested in animal models...

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..Therefore, monitoring these and additional genetic changes upon zoonotic infections is important. Identification of genetic changes responsible for transmission between mammals will be an important task for the near future...

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..We argue that wild bird screening can function as a sentinel system, and we give an example of how it could have been used to forecast a remote and deadly outbreak of influenza A in poultry...

..Hooded vultures could potentially be vectors or sentinels of influenza subtype H5N1, as are cats and swans elsewhere...

..The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent...

..This finding extends the host range of influenza virus and has implications for influenza virus epidemiology and wildlife conservation...

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..Further, this approach offers a route to predicting the relative success of emerging strains, which could be achieved by quantifying the combined effects of population level immune escape and viral fitness on strain evolution...

..The data suggest that a monoclonal antibody could be used prophylactically to prevent lower respiratory tract disease caused by hMPV...

..Efforts to develop broadly neutralizing vaccines against either HIV-1 or influenza virus might establish a paradigm for future vaccines against highly variable pathogens...

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..Because different names have been used to describe emerging lineages of the virus, this study describes a unified nomenclature system to facilitate discussion and comparison of subtype H5N1 lineages...

..These studies showed that b/h PIV3/hMPV F2 was immunogenic, protective and attenuated in non-human primates and warrants further evaluation in humans as a vaccine candidate for prevention of hMPV-associated respiratory tract diseases...

..Although these animal models do not mimic human hMPV disease signs, they will nevertheless be invaluable for the future evaluation of hMPV antivirals, mAbs and vaccines...

..In contrast to what has been found in North American studies; Eurasian spring migrating ducks passing through Sweden had a relatively high prevalence of influenza A virus...