Avian influenza, a permanent threat

The avian influenza virus belongs to the influenza type A genus. Each strain can be sub-typed for its surface proteins: hemagglutinin (HA) and neuraminidase (NA). Aquatic birds represent the natural reservoir of the virus and occasionally transmit it to domestic poultry. The clinical form of the disease depends on the pathotype of the circulating strain. Most infections with low pathogenic (LP) strains are asymptomatic whereas those with highly pathogenic (HP) strains induce fowl plague. HP strains emerge from LP ones by mutations and insertions in the HA gene. Avian influenza can be occasionally transmitted to mammals including human. Evolution of recent HP H5N1 strains toward an increased pathogenicity and a wider host spectrum is worrying, and experts fear that these new strains could give rise to the next human influenza pandemic. Vaccination with inactivated or recombinant vaccines can be used in addition to biosafety measures to contend an outbreak.L'agent responsable des grippes aviaires est le virus influenza de type A. Chaque souche virale peut être sous-typée pour les deux protéines de surface : l'hémagglutinine (HA) et la neuraminidase (NA). Les oiseaux aquatiques constituent le réservoir de ces virus et peuvent occasionnellement les transmettre aux volailles domestiques. Les grippes aviaires se manifestent sous plusieurs formes cliniques selon le pathotype des souches virales circulantes. Les souches faiblement pathogènes (FP) n'induisent le plus souvent qu'une infection asymptomatique tandis que les souches hautement pathogènes (HP) sont responsables de peste aviaire. Les souches HP émergent des souches FP de sous-type H5 ou H7 par mutation et insertion dans le gène de l'HA. Les virus influenza aviaire peuvent être occasionnellement transmis à des mammifères, y compris l'homme. L'évolution des souches HP H5N1 asiatiques récentes vers un pouvoir pathogène accru et un spectre d'hôte élargi est inquiétant, et les experts redoutent que ces souches soient à l'origine d'une nouvelle pandémie humaine. La vaccination au moyen de vaccins inactivés ou recombinés peut être utilisée en complément des mesures de biosécurité pour lutter contre une épizootie

Equine influenza: an update

Equine influenza is a contagious disease of the upper respiratory tract of horses caused by the influenza subtypes H3N8 or H7N7. The disease has spread worldwide helped by the international transport of horses. Influenza epidemics can have a significant economic impact as seen in Hong Kong in 1992. Rapid and sensitive diagnostic tests are needed to implement equine flu control programmes . Control is based on regular vaccination and management practices designed to reduce the risk of introducing and spreading the virus to susceptible horse populations. To guarantee the vaccine’s efficacy, the H3N8 strains used in the vaccine must be updated regularly with viruses isolated from the latest infection foci. In the past decade, new-generation vaccines, particularly modified live and recombinant vaccines, have become available to the horse industry and induce an immunity closer to that induced by wild strains.La grippe équine est une maladie contagieuse des voies respiratoires supérieures des équidés, causée par le virus grippal de sous-type H3N8 ou H7N7, ce dernier n'ayant plus été isolé depuis 20 ans. La maladie s'est propagée dans le monde entier à la faveur des mouvements internationaux de chevaux. Les épidémies de grippe équine peuvent avoir des répercussions économiques considérables, comme ce fut le cas en 1992 à Hong Kong. Les programmes de contrôle de la grippe équine requièrent l'utilisation de trousses de diagnostic sensibles et rapides. Le contrôle est basé sur la vaccination régulière et la gestion d'élevage avec comme objectif de limiter le risque d'introduction et de transmission du virus dans les populations équines sensibles. L'évolution des souches de grippe H3N8 nécessite une actualisation régulière des souches vaccinales avec les virus représentatifs des derniers foyers infectieux pour assurer l'efficacité continue des vaccins. Ces dix dernières années, des vaccins de nouvelle génération, en particulier des vaccins vivants atténués et des vaccins recombinés, ont été mis sur le marché et induisent une immunité plus proche de celle induite par les souches sauvages

Replication, Pathogenesis and Transmission of Pandemic (H1N1) 2009 Virus in Non-Immune Pigs

The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised important questions, including origin and host range [1,2]. Two of the three pandemics in the last century resulted in the spread of virus to pigs (H1N1, 1918; H3N2, 1968) with subsequent independent establishment and evolution within swine worldwide [3]. A key public and veterinary health consideration in the context of the evolving pandemic is whether the H1N1/09 virus could become established in pig populations [4]. We performed an infection and transmission study in pigs with A/California/07/09. In combination, clinical, pathological, modified influenza A matrix gene real time RT-PCR and viral genomic analyses have shown that infection results in the induction of clinical signs, viral pathogenesis restricted to the respiratory tract, infection dynamics consistent with endemic strains of influenza A in pigs, virus transmissibility between pigs and virus-host adaptation events. Our results demonstrate that extant H1N1/09 is fully capable of becoming established in global pig populations. We also show the roles of viral receptor specificity in both transmission and tissue tropism. Remarkably, following direct inoculation of pigs with virus quasispecies differing by amino acid substitutions in the haemagglutinin receptor-binding site, only virus with aspartic acid at position 225 (225D) was detected in nasal secretions of contact infected pigs. In contrast, in lower respiratory tract samples from directly inoculated pigs, with clearly demonstrable pulmonary pathology, there was apparent selection of a virus variant with glycine (225G). These findings provide potential clues to the existence and biological significance of viral receptor-binding variants with 225D and 225G during the 1918 pandemic [5]

Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

Lymphoid oncogenesis is a life threatening complication associated with a number of persistent viral infections (e.g. EBV and HTLV-1 in humans). With many of these infections it is difficult to study their natural history and the dynamics of tumor formation. Marek's Disease Virus (MDV) is a prevalent α-herpesvirus of poultry, inducing CD4+ TCRαβ+ T cell tumors in susceptible hosts. The high penetrance and temporal predictability of tumor induction raises issues related to the clonal structure of these lymphomas. Similarly, the clonality of responding CD8 T cells that infiltrate the tumor sites is unknown. Using TCRβ repertoire analysis tools, we demonstrated that MDV driven CD4+ T cell tumors were dominated by one to three large clones within an oligoclonal framework of smaller clones of CD4+ T cells. Individual birds had multiple tumor sites, some the result of metastasis (i.e. shared dominant clones) and others derived from distinct clones of transformed cells. The smaller oligoclonal CD4+ cells may represent an anti-tumor response, although on one occasion a low frequency clone was transformed and expanded after culture. Metastatic tumor clones were detected in the blood early during infection and dominated the circulating T cell repertoire, leading to MDV associated immune suppression. We also demonstrated that the tumor-infiltrating CD8+ T cell response was dominated by large oligoclonal expansions containing both “public” and “private” CDR3 sequences. The frequency of CD8+ T cell CDR3 sequences suggests initial stimulation during the early phases of infection. Collectively, our results indicate that MDV driven tumors are dominated by a highly restricted number of CD4+ clones. Moreover, the responding CD8+ T cell infiltrate is oligoclonal indicating recognition of a limited number of MDV antigens. These studies improve our understanding of the biology of MDV, an important poultry pathogen and a natural infection model of virus-induced tumor formation

The effectiveness of mass vaccination on Marek's disease virus (MDV) outbreaks and detection within a broiler barn: A modeling study

AbstractMarek's disease virus (MDV), a poultry pathogen, has been increasing in virulence since the mid twentieth century. Since multiple vaccines have been developed and widely implemented, losses due to MDV have decreased. However, vaccine failure has occurred in the past and vaccine breakthroughs remain a problem. Failure of disease control with current vaccines would have significant economic and welfare consequences. Nevertheless, the epidemiology of the disease during a farm outbreak is not well understood. Here we present a mathematical model to predict the effectiveness of vaccines to reduce the outbreak probability and disease burden within a barn. We find that the chance of an outbreak within a barn increases with the virulence of an MDV strain, and is significantly reduced when the flock is vaccinated, especially when there the contaminant strain is of low virulence. With low quantities of contaminated dust, there is nearly a 100% effectiveness of vaccines to reduce MDV outbreaks. However, the vaccine effectiveness drops to zero with an increased amount of contamination with a middle virulence MDV strain. We predict that the larger the barn, and the more virulent the MDV strain is, the more virus is produced by the time the flock is slaughtered. With the low-to-moderate virulence of the strains studied here, the number of deaths due to MDV is very low compared to all-cause mortality regardless of the vaccination status of the birds. However, the cumulative MD incidence can reach 100% for unvaccinated cohorts, and 35% for vaccinated cohorts. These results suggest that death due to MDV is an insufficient metric to assess the prevalence of MDV broiler barns regardless of vaccine status, such that active surveillance is required to successfully assess the probability of MDV outbreaks, and to limit transmission of MDV between successive cohorts of broiler chickens

Molecular Epidemiology and Evolution of Influenza Viruses Circulating within European Swine between 2009 and 2013

The emergence in humans of the A(H1N1)pdm09 influenza virus, a complex reassortant virus of swine origin, highlighted the importance of worldwide influenza virus surveillance in swine. To date, large-scale surveillance studies have been reported for southern China and North America, but such data have not yet been described for Europe. We report the first large-scale genomic characterization of 290 swine influenza viruses collected from 14 European countries between 2009 and 2013. A total of 23 distinct genotypes were identified, with the 7 most common comprising 82% of the incidence. Contrasting epidemiological dynamics were observed for two of these genotypes, H1huN2 and H3N2, with the former showing multiple long-lived geographically isolated lineages, while the latter had short-lived geographically diffuse lineages. At least 32 human-swine transmission events have resulted in A(H1N1)pdm09 becoming established at a mean frequency of 8% across European countries. Notably, swine in the United Kingdom have largely had a replacement of the endemic Eurasian avian virus-like (“avian-like”) genotypes with A(H1N1)pdm09-derived genotypes. The high number of reassortant genotypes observed in European swine, combined with the identification of a genotype similar to the A(H3N2)v genotype in North America, underlines the importance of continued swine surveillance in Europe for the purposes of maintaining public health. This report further reveals that the emergences and drivers of virus evolution in swine differ at the global level.IMPORTANCE The influenza A(H1N1)pdm09 virus contains a reassortant genome with segments derived from separate virus lineages that evolved in different regions of the world. In particular, its neuraminidase and matrix segments were derived from the Eurasian avian virus-like (“avian-like”) lineage that emerged in European swine in the 1970s. However, while large-scale genomic characterization of swine has been reported for southern China and North America, no equivalent study has yet been reported for Europe. Surveillance of swine herds across Europe between 2009 and 2013 revealed that the A(H1N1)pdm09 virus is established in European swine, increasing the number of circulating lineages in the region and increasing the possibility of the emergence of a genotype with human pandemic potential. It also has implications for veterinary health, making prevention through vaccination more challenging. The identification of a genotype similar to the A(H3N2)v genotype, causing zoonoses at North American agricultural fairs, underlines the importance of continued genomic characterization in European swine

European Surveillance Network for Influenza in Pigs : Surveillance Programs, Diagnostic Tools and Swine Influenza Virus Subtypes Identified in 14 European Countries from 2010 to 2013

Swine influenza causes concern for global veterinary and public health officials. In continuing two previous networks that initiated the surveillance of swine influenza viruses (SIVs) circulating in European pigs between 2001 and 2008, a third European Surveillance Network for Influenza in Pigs (ESNIP3, 2010-2013) aimed to expand widely the knowledge of the epidemiology of European SIVs. ESNIP3 stimulated programs of harmonized SIV surveillance in European countries and supported the coordination of appropriate diagnostic tools and subtyping methods. Thus, an extensive virological monitoring, mainly conducted through passive surveillance programs, resulted in the examination of more than 9 000 herds in 17 countries. Influenza A viruses were detected in 31% of herds examined from which 1887 viruses were preliminary characterized. The dominating subtypes were the three European enzootic SIVs: avian-like swine H1N1 (53.6%), human-like reassortant swine H1N2 (13%) and human-like reassortant swine H3N2 (9.1%), as well as pandemic A/H1N1 2009 (H1N1pdm) virus (10.3%). Viruses from these four lineages co-circulated in several countries but with very different relative levels of incidence. For instance, the H3N2 subtype was not detected at all in some geographic areas whereas it was still prevalent in other parts of Europe. Interestingly, H3N2-free areas were those that exhibited highest frequencies of circulating H1N2 viruses. H1N1pdm viruses were isolated at an increasing incidence in some countries from 2010 to 2013, indicating that this subtype has become established in the European pig population. Finally, 13.9% of the viruses represented reassortants between these four lineages, especially between previous enzootic SIVs and H1N1pdm. These novel viruses were detected at the same time in several countries, with increasing prevalence. Some of them might become established in pig herds, causing implications for zoonotic infections