Influenza is a highly contagious respiratory pathogen that continues to evolve and threaten both veterinary and human public health. Influenza A viruses are continually undergoing molecular changes through mutations, reassortment, and, in rare instances, recombination. While they generally cause benign enteric infection in their natural reservoir of wild aquatic birds, they can cause catastrophic and potentially lethal disease outbreaks in humans, domestic poultry, and pigs when they cross the host species barrier. The continuing circulation of highly pathogenic (HP) H5N1 influenza viruses in domestic poultry in parts of Eurasia and the emergence and global spread of pandemic H1N1 2009 are current examples of influenza evolution. The spread of both HP H5N1 and pandemic H1N1 to multiple hosts emphasizes the potential for continued evolution. In this review, we discuss the current understanding of influenza A virus structure and strategies of variation, with a specific focus on the HP H5N1 and pandemic H1N1 influenza viruses. Additionally, we attempt to identify the gaps in our knowledge of H5N1 and pandemic H1N1 influenza viruses. These gaps include (i) an understanding of the molecular determinants of influenza virus and the host that permit efficient transmissibility and pandemic potential, (ii) the urgent need for prospective surveillance in apparently healthy swine, (iii) the molecular determinants of high pathogenicity in poultry, pigs, and people, (iv) the genetic basis of host susceptibility, (v) antigenic variability, (vi) the use of vaccine to control influenza, (vii) the role of wild birds as the reservoir of highly pathogenic avian influenza, (viii) the problems with vaccines, (ix) seasonality, (x) co-infections, and (xi) anti-influenza drug resistance. Our failure to eradicate HP H5N1 globally and to explain why H5N1 does not transmit efficiently in humans while an H1N1 pandemic virus of swine origin spread globally in months are key examples that emphasize the critical need to bridge these knowledge gaps. Future directions in influenza research that will help us resolve each of the above-mentioned knowledge gaps include complete genomic and proteomic analysis of both the virus and the host with the prospect of designing new control strategies and the development of genetically resistant hosts.

Avian influenza (AI) virus is one of the most important diseases of the poultry industry around the world. The virus has a broad host range in birds and mammals, although the natural reservoir is wild birds where it typically causes an asymptomatic to mild infection. The virus in poultry can cause a range of clinical diseases and is defined either as low pathogenic AI (LPAI) or highly pathogenic AI (HPAI) depending on the type of disease it causes in chickens. Viruses that replicate primarily on mucosal surfaces and cause mild disease with low mortality are termed LPAI. Viruses that replicate on mucosal surfaces and systemically and cause severe disease with a mortality rate of 75% or greater in experimentally infected chickens are referred to as HPAI. A virus that is highly pathogenic in chickens may infect but result in a completely different disease and replication pattern in other host species. Outbreaks of HPAI have been relatively uncommon around the world in the last 50 years and have had limited spread within a country or region with one major exception, Asian lineage H5N1 that was first identified in 1996. This lineage of virus has spread to over 60 countries and has become endemic in poultry in at least four countries. AI virus also represents a public health threat, with some infected humans having severe disease and with a high case fatality rate. AI remains a difficult disease to control because of the highly infectious nature of the virus and the interface of domestic and wild animals. A better understanding of the disease and its transmission is important for control.

This paper takes a closer look at three interrelated areas of study: avian host biology, the role of human activities in virus transmission, and the surveillance activities centered on avian influenza in wild birds. There are few ecosystems in which birds are not found. Correspondingly, avian influenza viruses are equally global in distribution, relying on competent avian hosts. The immune systems, annual cycles, feeding behaviors, and migration patterns of these hosts influence the ecology of the disease. Decreased biodiversity has also been linked to heightened disease transmission in several disease systems, and it is evident that active destruction and modification of wetland environments for human use is impacting avian populations drastically. Legal and illegal trade in wild birds present a significant risk for introduction and maintenance of exotic diseases. After the emergence of HPAI H5N1 in Hong Kong in 1996 and the ensuing geographic spread of outbreaks after 2003, both infected countries and those at risk of introduction began intensifying avian influenza surveillance efforts. Several techniques for sampling wild birds for influenza viruses have been applied. Benefits, problems, and biases exist for each method. The wild bird avian influenza surveillance programs taking place across the continents are now scaling back due to the rise of other spending priorities; hopefully the lessons learned from this work will be preserved and will inform future research and disease outbreak response priorities.

In the past decade, the pandemics of highly pathogenic avian influenza H5N1 and the novel H1N1 influenza have both illustrated the potential of influenza viruses to rapidly emerge and spread widely in animals and people. Since both of these viruses are zoonotic, these pandemics have been the driving force behind a renewed commitment by the medical and veterinary professions to practice One World, One Health for the control of infectious diseases. The discovery in 2004 that an equine origin H3N8 influenza virus was the cause of an extensive epidemic of respiratory disease in dogs in the USA came as a surprise; at that time dogs were thought to be refractory to infection with influenza viruses. In 2007, a second emerging canine influenza was confirmed in Korea, but this time the causal virus was an H3N2 avian influenza virus. This review focuses on recent events associated with equine and canine influenza viruses. While these viruses do not appear to be zoonotic, the close association between humans and dogs, and to a lesser extent horses, demands that we develop better surveillance and control strategies for emerging diseases in companion animals within the context of One World, One Health.

Influenza A viruses are enveloped viruses belonging to the family Orthomyxoviridae that encompasses four more genera: Influenza B, Influenza C, Isavirus and Thogotovirus. Type A viruses belong to the only genus that is highly infectious to a variety of mammalian and avian species. They are divided into subtypes based on two surface glycoproteins, the hemagglutinin (HA) and neuraminidase (NA). So far, 16 HA and 9 NA subtypes have been identified worldwide, making a possible combination of 144 subtypes between both proteins. Generally, individual viruses are host-specific, however, interspecies transmission of influenza A viruses is not uncommon. All of the HA and NA subtypes have been isolated from wild birds; however, infections in humans and other mammalian species are limited to a few subtypes. The replication of individual influenza A virus in a specific host is dependent on many factors including, viral proteins, host system and environmental conditions. In this review, the key findings that contribute to the transmission of influenza A viruses amongst different species are summarized.

Emerging infectious diseases are critical issues of public health and the economic and social stability of nations. As demonstrated by the international response to the severe acute respiratory syndrome (SARS) and influenza A, rapid genomic sequencing is a crucial tool to understand diseases that occur at the interface of human and animal populations. However, our ability to make sense of sequence data lags behind our ability to acquire the data. The potential of sequence data on pathogens is not fully realized until raw data are translated into public health intelligence. Sequencing technologies have become highly mechanized. If the political will for data sharing remains strong, the frontier for progress in emerging infectious diseases will be in analysis of sequence data and translation of results into better public health science and policy. For example, applying analytical tools such as Supramap (http://supramap.osu.edu) to genomic data for pathogens, public health scientists can track specific mutations in pathogens that confer the ability to infect humans or resist drugs. The results produced by the Supramap application are compelling visualizations of pathogen lineages and features mapped into geographic information systems that can be used to test hypotheses and to follow the spread of diseases across geography and hosts and communicate the results to a wide audience.

Swine influenza is an important contagious disease in pigs caused by influenza A viruses. Although only three subtypes of influenza A viruses, H1N1, H1N2 and H3N2, predominantly infect pigs worldwide, it is still a big challenge for vaccine manufacturers to produce efficacious vaccines for the prevention and control of swine influenza. Swine influenza viruses not only cause significant economic losses for the swine industry, but are also important zoonotic pathogens. Vaccination is still one of the most important and effective strategies to prevent and control influenza for both the animal and human population. In this review, we will discuss the current status of swine influenza worldwide as well as current and future options to control this economically important swine disease.