Pathogenicity And Transmissibility Of H3n8 Equine Influenza Viruses

Equine influenza H3N8 virus (EIV) jumped into dogs around the year 2000 and consequently caused the emergence of canine influenza H3N8 virus (CIV). This dog-specific virus has since been circulating primarily in the United States in animal shelters and places with high density dog populations. Host specificity and adaptation of influenza A viruses (IAVs) are not well understood, and so we compared the biological properties of EIV and CIV in order to further elucidate these properties. We used a variety of assays to characterize virus growth, infections in different host cells, receptor specificity, hemagglutinin (HA) cleavage, and infections in tracheal cultures. Despite numerous mutations between the genomes, we found minimal biological differences comparing EIV and CIV. Both viruses grew similarly in dog cells (MDCK) while they could not infect horse (EQKD) and human (A549) cells. Both viruses' receptor binding HA protein preferred [alpha]2-3 over [alpha]2-6 linked sialic acids, and there was also no difference comparing HA cleavage efficiency. Interestingly, infections in tracheal cultures showed CIV could not establish a productive infection in horse trachea compared to EIV. We also characterized an ancillary protein, PA-X, from both viruses by using reporter assays and RNA sequencing (RNA-seq). Reporter assays showed EIV and CIV PA-X had ribonuclease activity and suppressed [beta]-galactosidase and GFP expression. Notably, EIV PA-X had significantly stronger activity compared to CIV PA-X. Using site directed mutagenesis we found this difference was due to a mutation at amino acid position 231 and the truncation at the C- terminus. RNA-seq of cells transfected with plasmids encoding EIV and CIV PA-X revealed that they up-regulated the expression of many host genes compared to the controls. These altered genes were involved in various functions such as modulating the immune response, protein ubiquitination, ER-Golgi sorting and trafficking, and transcription. The RNA-seq analysis did not reveal any differences in gene expression comparing EIV and CIV PA-X samples however. Taken together our results showed EIV and CIV's biology was very similar despite many genetic differences between the two viruses, and this implies IAV host-switching and adaptation may be mediated by more subtle factors.

The equine influenza virus (EIV) is a major pathogen of respiratory diseases in horses, donkeys and mules. Equine influenza (EI) is characterized by a very rapid spread and remains a disease with high economic stakes for the equine industry. A large-scale outbreak caused by equine influenza virus of the H3N8 subtype has occurred in each decade since an H3N8 was first isolated from horses in 1963. Each epidemic, and some minor outbreaks, has influenced equine influenza surveillance and vaccination policies in the world. The use of the molecular tools is of a high interest in epidemiology. The interest of the association of these techniques and the classical epidemiological analyses will be illustrated by taking the example of equine influenza viruses. The determination and the comparison of the nucleotide sequences allow to characterize the virus strains more precisely than the classical methods and are useful to analyze the evolution of the equine influenza viruses. These methods are also useful to select the relevant strains that will be used in the vaccines. The possible reasons for the infection of horses despite intensive vaccination are currently being investigated and may shed new light on the epidemiology of equine influenza.

Influenza virus is an infectious pathogen causing significant respiratory signs and its infection has been a constant burden of global public health. Unique characteristics of influenza virus poses a challenge to investigate transmission dynamics using conventional epidemiological approaches on statistical inference on a host scale. First, evolutionary change of influenza virus in key antigenic sites impacts on the effectiveness of preventive and control program. Second, current complexity of hosts' movement addresses a difficulty in tracing transmission of infectious strains and intensified the potential of pandemic influenza outbreaks. Third, dynamics of influenza virus infection in wild host species complicates the identification of novel influenza spillover into other host species such as human and livestock. This epidemiological study implemented multi-scale multidisciplinary approaches to evaluate the transmission dynamics of influenza virus in horse and bird populations. In the first chapter, we evaluated the evolutionary characteristics of equine influenza virus (EIV) H3N8 strains detected in the United States (US) from 2012 to 2017 using phylogenetic and bioinformatic tools. Almost all US strains belonged to currently dominant FC1 clade and accumulated nucleotide substitutions in key antigenic regions of HA gene under heterogenous positive selection by sites. These findings revealed that antigenic drift in the HA gene of field strains in the US likely impacted on the evasion of vaccine-induced immunity and reduced the contemporary vaccine protection in US horse population. The second chapter predicted the pattern of EIV H3N8 spread on a US and global scale by phylodynamic approaches. Global phylogeography found that most novel strains originated EIV lineage in North America and spread to other global regions. US phylogeography predicted that southern and midwestern strains were mostly likely source of novel strains in the US horse population. EIV H3N8 changed approximately three nucleotides per year in HA gene consistently, which likely formed antigenic drift of global EIV strains. In the third chapter of my study, we estimated the habitat use of wild migratory waterfowl over four migration cycles in the Republic of Korea from 2013 to 2016 based on tracking records of fine-scale tracking device. Our study revealed that commercial poultry farms located within the habitat of wild waterfowl showed significantly higher risk for highly pathogenic avian influenza (HPAI) outbreaks compared to poultry farms outside of the habitat. These finding indicated that wildlife-domestic interface likely impacted on the novel HPAI spillover into domestic poultry farms. Overall, the three chapters of my study not only provided valuable insights about influenza virus infection dynamics but also illustrated how integration of multi-scale multidisciplinary epidemiological approaches can be used to address complex epidemiological problems. Ultimately, my research will better support global disease surveillance and more cost-effectively prevent and control influenza pandemics or other emerging and re-emerging diseases at the wildlife-domestic-human interface.

Human sufferings, including deaths, can be reduced or avoided by applying routine principles of hygiene in individuals' lives. Some hygiene routines are purely simple remedies, which are inexpensive, affordable, acceptable and easily accessible. It is evident that change is first enacted from within the mindset of an individual, then transmitted to families, groups and communities, and eventually the mindset of a nation can change creating an environment which is better for everybody to live in. This book contains chapters discussing conditions or diseases that may not be common in the readers' area. Caution as such may never be underestimated considering the fact that we are living in a global village where one can never say 'this does not occur in my area' but rather question, does this occur in my community, why does it occur, who is affected, where and when does it occur and what can be done about it? These questions constitute what epidemiology is all about, and their precise and comprehensive answers can transform lives and help us have the right perceptions for the health challenges we face and accept the possibility of dealing with them directly.

Animal Influenza, Second Edition is a comprehensive text on animal influenza. Organized by species, coverage includes avian, swine, equine and mammals, with each section including data on influenza viruses, the infection and disease they cause, and strategies used in control. Covers the full range of topics within avian, swine, equine and mammalian influenzas in one comprehensive and authoritative text Provides a summarization of peer-reviewed and empirical data on influenza viruses, the infection, and diseases they cause Discusses strategies used in control of the disease Leading experts are drawn together to provide an international and multi-disciplinary perspective Fuses latest developments in basic scientific research with practical guidance on management of the disease

The Food and Agriculture Organization of the United Nations has recently estimated that the world equid population exceeds 110 million. Working equids (horses, ponies, donkeys, and mules) remain essential to ensure the livelihood of poor communities around the world. In many developed countries, the equine industry has significant economical weight, with around 7 million horses in Europe alone. The close relationship between humans and equids and the fact that the athlete horse is the terrestrial mammal that travels the most worldwide after humans are important elements to consider in the transmission of pathogens and diseases, amongst equids and to other species. The potential effect of climate change on vector ecology and vector-borne diseases is also of concern for both human and animal health. In this Special Issue, we intend to explore our understanding of a panel of equine viruses, looking at their pathogenicity, their importance in terms of welfare and potential association with diseases, their economic importance and impact on performance, and how their identification can be helped by new technologies and methods.

This title is directed primarily towards health care professionals outside of the United States. Equine Respiratory Medicine and Surgery provides up-to-date, in-depth coverage of the diagnosis and management of respiratory disorders in the horse. It discusses respiratory physiology and examination techniques, as well as a review of the medical and surgical problems that may be encountered, organized anatomically and progressing in logical fashion from the upper airways, larynx and sinuses, through the lower airways, the lungs, and diaphragm. Common conditions covered include infections, allergy, trauma, cysts, and tumors. High quality artwork, including relevant radiographic and ultrasonographic images, CAT scans, MRI images, and color photographs aid understanding and diagnosis. A truly international perspective includes guidelines for different geographic areas and racing jurisdictions. Features in-depth coverage of the role of the veterinarian in the management of athletic horses with respiratory tract diseases.