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Nicola S Lewis,
Zurab Javakhishvili, Colin A Russell,
Ann Machablishvili,
Pascal Lexmond,
Josanne H Verhagen,
Oanh Vuong,
Tinatin Onashvili,
Marina Donduashvili,
Derek J Smith,
Ron A M Fouchier
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ABSTRACT: The Caucasus, at the border of Europe and Asia, is important for migration and over-wintering of wild waterbirds. Three flyways, the Central Asian, East Africa-West Asia, and Mediterranean/Black Sea flyways, converge in the Caucasus region. Thus, the Caucasus region might act as a migratory bridge for influenza virus transmission when birds aggregate in high concentrations in the post-breeding, migrating and overwintering periods. Since August 2009, we have established a surveillance network for influenza viruses in wild birds, using five sample areas geographically spread throughout suitable habitats in both eastern and western Georgia. We took paired tracheal and cloacal swabs and fresh feces samples. We collected 8343 swabs from 76 species belonging to 17 families in 11 orders of birds, of which 84 were real-time RT-PCR positive for avian influenza virus (AIV). No highly pathogenic AIV (HPAIV) H5 or H7 viruses were detected. The overall AIV prevalence was 1.6%. We observed peak prevalence in large gulls during the autumn migration (5.3-9.8%), but peak prevalence in Black-headed Gulls in spring (4.2-13%). In ducks, we observed increased AIV prevalence during the autumn post-moult aggregations and migration stop-over period (6.3%) but at lower levels to those observed in other more northerly post-moult areas in Eurasia. We observed another prevalence peak in the overwintering period (0.14-5.9%). Serological and virological monitoring of a breeding colony of Armenian Gulls showed that adult birds were seropositive on arrival at the breeding colony, but juveniles remained serologically and virologically negative for AIV throughout their time on the breeding grounds, in contrast to gull AIV data from other geographic regions. We show that close phylogenetic relatives of viruses isolated in Georgia are sourced from a wide geographic area throughout Western and Central Eurasia, and from areas that are represented by multiple different flyways, likely linking different host sub-populations.
PLoS ONE 01/2013; 8(3):e58534. · 4.09 Impact Factor
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Colin A Russell,
Judith M Fonville,
André E X Brown,
David F Burke,
David L Smith,
Sarah L James,
Sander Herfst,
Sander van Boheemen,
Martin Linster,
Eefje J Schrauwen,
Leah Katzelnick,
Ana Mosterín,
Thijs Kuiken,
Eileen Maher,
Gabriele Neumann,
Albert D M E Osterhaus,
Yoshihiro Kawaoka,
Ron A M Fouchier,
Derek J Smith
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ABSTRACT: Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat.
Science 06/2012; 336(6088):1541-7. · 31.20 Impact Factor
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Kim B Westgeest,
Miranda de Graaf,
Mathieu Fourment,
Theo M Bestebroer,
Ruud van Beek,
Monique I J Spronken,
Jan C de Jong,
Guus F Rimmelzwaan, Colin A Russell,
Albert D M E Osterhaus,
Gavin J D Smith,
Derek J Smith,
Ron A M Fouchier
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ABSTRACT: Each year, influenza viruses cause epidemics by evading pre-existing humoral immunity through mutations in the major glycoproteins: the haemagglutinin (HA) and the neuraminidase (NA). In 2004, the antigenic evolution of HA of human influenza A (H3N2) viruses was mapped (Smith et al., Science 305, 371-376, 2004) from its introduction in humans in 1968 until 2003. The current study focused on the genetic evolution of NA and compared it with HA using the dataset of Smith and colleagues, updated to the epidemic of the 2009/2010 season. Phylogenetic trees and genetic maps were constructed to visualize the genetic evolution of NA and HA. The results revealed multiple reassortment events over the years. Overall rates of evolutionary change were lower for NA than for HA1 at the nucleotide level. Selection pressures were estimated, revealing an abundance of negatively selected sites and sparse positively selected sites. 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.
Journal of General Virology 06/2012; 93(Pt 9):1996-2007. · 3.36 Impact Factor
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ABSTRACT: Seasonal epidemics caused by influenza virus are driven by antigenic changes (drift) in viral surface glycoproteins that allow evasion from preexisting humoral immunity. Antigenic drift is a feature of not only the hemagglutinin (HA), but also of neuraminidase (NA). We have evaluated the antigenic evolution of each protein in H1N1 and H3N2 viruses used in vaccine formulations during the last 15 y by analysis of HA and NA inhibition titers and antigenic cartography. As previously shown for HA, genetic changes in NA did not always lead to an antigenic change. The noncontinuous pattern of NA drift did not correspond closely with HA drift in either subtype. Although NA drift was demonstrated using ferret sera, we show that these changes also impact recognition by NA-inhibiting antibodies in human sera. Remarkably, a single point mutation in the NA of A/Brisbane/59/2007 was primarily responsible for the lack of inhibition by polyclonal antibodies specific for earlier strains. These data underscore the importance of NA inhibition testing to define antigenic drift when there are sequence changes in NA.
Proceedings of the National Academy of Sciences 12/2011; 108(51):20748-53. · 9.68 Impact Factor
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Alessio Lorusso,
Amy L Vincent,
Michelle L Harland,
David Alt,
Darrell O Bayles,
Sabrina L Swenson,
Marie R Gramer, Colin A Russell,
Derek J Smith,
Kelly M Lager,
Nicola S Lewis
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ABSTRACT: Prior to the introduction of the 2009 pandemic H1N1 virus from humans into pigs, four phylogenetic clusters (α-, β-, γ- and δ) of the haemagglutinin (HA) gene from H1 influenza viruses could be found in US swine. Information regarding the antigenic relatedness of the H1 viruses was lacking due to the dynamic and variable nature of swine lineage H1. We characterized 12 H1 isolates from 2008 by using 454 genome-sequencing technology and phylogenetic analysis of all eight gene segments and by serological cross-reactivity in the haemagglutination inhibition (HI) assay. Genetic diversity was demonstrated in all gene segments, but most notably in the HA gene. The gene segments from the 2009 pandemic H1N1 formed clusters separate from North American swine lineage viruses, suggesting progenitors of the pandemic virus were not present in US pigs immediately prior to 2009. Serological cross-reactivity paired with antigenic cartography demonstrated that the viruses in the different phylogenetic clusters are also antigenically divergent.
Journal of General Virology 12/2010; 92(Pt 4):919-30. · 3.36 Impact Factor
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Salin Chutinimitkul,
Sander Herfst,
John Steel,
Anice C Lowen,
Jianqiang Ye,
Debby van Riel,
Eefje J A Schrauwen,
Theo M Bestebroer,
Björn Koel,
David F Burke, [......],
Derek J Smith,
Marcel Jonges,
Adam Meijer,
Marion Koopmans,
Guus F Rimmelzwaan,
Thijs Kuiken,
Albert D M E Osterhaus,
Adolfo Garcia-Sastre,
Daniel R Perez,
Ron A M Fouchier
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ABSTRACT: The clinical impact of the 2009 pandemic influenza A(H1N1) virus (pdmH1N1) has been relatively low. However, amino acid substitution D222G in the hemagglutinin of pdmH1N1 has been associated with cases of severe disease and fatalities. D222G was introduced in a prototype pdmH1N1 by reverse genetics, and the effect on virus receptor binding, replication, antigenic properties, and pathogenesis and transmission in animal models was investigated. pdmH1N1 with D222G caused ocular disease in mice without further indications of enhanced virulence in mice and ferrets. pdmH1N1 with D222G retained transmissibility via aerosols or respiratory droplets in ferrets and guinea pigs. The virus displayed changes in attachment to human respiratory tissues in vitro, in particular increased binding to macrophages and type II pneumocytes in the alveoli and to tracheal and bronchial submucosal glands. Virus attachment studies further indicated that pdmH1N1 with D222G acquired dual receptor specificity for complex α2,3- and α2,6-linked sialic acids. Molecular dynamics modeling of the hemagglutinin structure provided an explanation for the retention of α2,6 binding. 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.
Journal of Virology 11/2010; 84(22):11802-13. · 5.40 Impact Factor
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Rebecca J Garten,
C Todd Davis, Colin A Russell,
Bo Shu,
Stephen Lindstrom,
Amanda Balish,
Wendy M Sessions,
Xiyan Xu,
Eugene Skepner,
Varough Deyde, [......],
Ruben Donis,
Jacqueline Katz,
Lyn Finelli,
Carolyn B Bridges,
Michael Shaw,
Daniel B Jernigan,
Timothy M Uyeki,
Derek J Smith,
Alexander I Klimov,
Nancy J Cox
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ABSTRACT: Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests that the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting that previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).
Science 06/2009; 325(5937):197-201. · 31.20 Impact Factor
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Neil A Bryant,
Adam S Rash, Colin A Russell,
Julie Ross,
Annie Cooke,
Samantha Bowman,
Shona MacRae,
Nicola S Lewis,
Romain Paillot,
Reto Zanoni,
Hanspeter Meier,
Lowri A Griffiths,
Janet M Daly,
Ashish Tiwari,
Thomas M Chambers,
J Richard Newton,
Debra M Elton
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ABSTRACT: Equine influenza virus (EIV) surveillance is important in the management of equine influenza. It provides data on circulating and newly emerging strains for vaccine strain selection. To this end, antigenic characterisation by haemaggluttination inhibition (HI) assay and phylogenetic analysis was carried out on 28 EIV strains isolated in North America and Europe during 2006 and 2007. In the UK, 20 viruses were isolated from 28 nasopharyngeal swabs that tested positive by enzyme-linked immunosorbent assay. All except two of the UK viruses were characterised as members of the Florida sublineage with similarity to A/eq/Newmarket/5/03 (clade 2). One isolate, A/eq/Cheshire/1/06, was characterised as an American lineage strain similar to viruses isolated up to 10 years earlier. A second isolate, A/eq/Lincolnshire/1/07 was characterised as a member of the Florida sublineage (clade 1) with similarity to A/eq/Wisconsin/03. Furthermore, A/eq/Lincolnshire/1/06 was a member of the Florida sublineage (clade 2) by haemagglutinin (HA) gene sequence, but appeared to be a member of the Eurasian lineage by the non-structural gene (NS) sequence suggesting that reassortment had occurred. A/eq/Switzerland/P112/07 was characterised as a member of the Eurasian lineage, the first time since 2005 that isolation of a virus from this lineage has been reported. Seven viruses from North America were classified as members of the Florida sublineage (clade 1), similar to A/eq/Wisconsin/03. In conclusion, a variety of antigenically distinct EIVs continue to circulate worldwide. Florida sublineage clade 1 viruses appear to predominate in North America, clade 2 viruses in Europe.
Veterinary Microbiology 04/2009; 138(1-2):41-52. · 3.33 Impact Factor
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ABSTRACT: Influenza viruses are classic examples of antigenically variable pathogens and have a seemingly endless capacity to evolve in order to evade the immune response. The degree to which immunity induced by one strain is effective against another is mostly dependent on the antigenic difference between the strains. Antigenic drift is thus both the root cause of the enormous public health burden of influenza epidemics, and a primary reason why the virus is such a fascinating pathogen from a scientific perspective. Antigenic cartography is a new technique that can be used to analyse binding assay data and to obtain a detailed quantitative visualization of antigenic differences among pathogens. We provide a brief summary of antigenic cartography and its use to analyse the antigenic drift of influenza A(H3N2) viruses in humans and swine
05/2008: pages 32 - 44; , ISBN: 9780470770672
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Colin A Russell,
Terry C Jones,
Ian G Barr,
Nancy J Cox,
Rebecca J Garten,
Vicky Gregory,
Ian D Gust,
Alan W Hampson,
Alan J Hay,
Aeron C Hurt, [......],
Masatsugu Obuchi,
Takato Odagiri,
Albert D M E Osterhaus,
Guus F Rimmelzwaan,
Michael W Shaw,
Eugene Skepner,
Klaus Stohr,
Masato Tashiro,
Ron A M Fouchier,
Derek J Smith
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ABSTRACT: Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.
Science 05/2008; 320(5874):340-6. · 31.20 Impact Factor
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ABSTRACT: Rabies control in terrestrial wildlife reservoirs relies heavily on an oral rabies vaccine (ORV). In addition to direct ORV delivery to protect wildlife in natural habitats, vaccine corridors have been constructed to control the spread; these corridors are often developed around natural barriers, such as rivers, to enhance the effectiveness of vaccine deployment. However, the question of how to optimally deploy ORV around a river (or other natural barrier) to best exploit the barrier for rabies control has not been addressed using mathematical models. Given an advancing epidemic wave, should the vaccine be distributed on both sides of barrier, behind the barrier, or in front of it? Here, we introduce a new mathematical model for the dynamics of raccoon rabies on a spatially heterogeneous landscape that is both simple and realistic. We demonstrate that the vaccine should always be deployed behind a barrier to minimize the recurrence of subsequent epidemics. Although the oral rabies vaccine is sufficient to induce herd immunity inside the vaccinated area, it simultaneously creates a demographic refuge. When that refuge is in front of a natural barrier, seasonal dispersal from the vaccine corridor into an endemic region sustains epidemic oscillations of raccoon rabies. When the vaccine barrier creates a refuge behind the river, the low permeability of the barrier to host movement limits dispersal of the host population from the protected populations into the rabies endemic area and limits subsequent rabies epidemics.
PLoS ONE 02/2006; 1:e27. · 4.09 Impact Factor
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ABSTRACT: Rabies is an important public health concern in North America because of recent epidemics of a rabies virus variant associated with raccoons. The costs associated with surveillance, diagnostic testing, and post-exposure treatment of humans exposed to rabies have fostered coordinated efforts to control rabies spread by distributing an oral rabies vaccine to wild raccoons. Authorities have tried to contain westward expansion of the epidemic front of raccoon-associated rabies via a vaccine corridor established in counties of eastern Ohio, western Pennsylvania, and West Virginia. Although sporadic cases of rabies have been identified in Ohio since oral rabies vaccine distribution in 1998, the first evidence of a significant breach in this vaccine corridor was not detected until 2004 in Lake County, Ohio. Herein, we forecast the spatial spread of rabies in Ohio from this breach using a stochastic spatial model that was first developed for exploratory data analysis in Connecticut and next used to successfully hind-cast wave-front dynamics of rabies spread across New York. The projections, based on expansion from the Lake County breach, are strongly affected by the spread of rabies by rare, but unpredictable long-distance translocation of rabid raccoons; rabies may traverse central Ohio at a rate 2.5-fold greater than previously analyzed wildlife epidemics. Using prior estimates of the impact of local heterogeneities on wave-front propagation and of the time lag between surveillance-based detection of an initial rabies case to full-blown epidemic, specific regions within the state are identified for vaccine delivery and expanded surveillance effort.
PLoS Biology 04/2005; 3(3):e88. · 11.45 Impact Factor
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ABSTRACT: Directly transmitted infectious diseases spread through wildlife populations as travelling waves away from the sites of original introduction. These waves often become distorted through their interaction with environmental and population heterogeneities and by long-distance translocation of infected individuals. Accurate a priori predictions of travelling waves of infection depend upon understanding and quantifying these distorting factors. We assess the effects of anisotropies arising from the orientation of rivers in relation to the direction of disease-front propagation and the damming effect of mountains on disease movement in natural populations. The model successfully predicts the local and large-scale prevaccination spread of raccoon rabies through New York State, based on a previous spatially heterogeneous model of raccoon-rabies invasion across the state of Connecticut. Use of this model provides a rare example of a priori prediction of an epidemic invasion over a naturally heterogeneous landscape. Model predictions matched to data can also be used to evaluate the most likely points of disease introduction. These results have general implications for predicting future pathogen invasions and evaluating potential containment strategies.
Proceedings of the Royal Society B: Biological Sciences 02/2004; 271(1534):21-5. · 5.41 Impact Factor
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Colin A. Russell,
Terry C. Jones,
Ian G. Barr,
Nancy J. Cox,
Rebecca J. Garten,
Vicky Gregory,
Ian D. Gust,
Alan W. Hampson,
Alan J. Hay,
Aeron C. Hurt, [......],
Masatsugu Obuchi,
Takato Odagiri,
Albert D.M.E. Osterhaus,
Guus F. Rimmelzwaan,
Michael W. Shaw,
Eugene Skepner,
Klaus Stohr,
Masato Tashiro,
Ron A.M. Fouchier,
Derek J. Smith
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ABSTRACT: Annual influenza epidemics in humans affect 5–15% of the population, causing an estimated half million deaths worldwide per year [Stohr K. Influenza—WHO cares. Lancet Infectious Diseases 2002;2(9):517]. The virus can infect this proportion of people year after year because the virus has an extensive capacity to evolve and thus evade the immune response. For example, since the influenza A(H3N2) subtype entered the human population in 1968 the A(H3N2) component of the influenza vaccine has had to be updated almost 30 times to track the evolution of the viruses and remain effective. The World Health Organization Global Influenza Surveillance Network (WHO GISN) tracks and analyzes the evolution and epidemiology of influenza viruses for the primary purpose of vaccine strain selection and to improve the strain selection process through studies aimed at better understanding virus evolution and epidemiology. Here we give an overview of the strain selection process and outline recent investigations into the global migration of seasonal influenza viruses.
Vaccine.
