Spread, diagnosis, and pathogenesis of swine influenza on modern farms

Despite extensive planning for the next influenza pandemic in humans, nature has once again confounded the influenza experts. The emergence and development of an H1N1 pandemic strain while an H1N1 virus was still circulating in humans is an unprecedented event. Here, we examine the emergence of H1N1 influenza viruses in the USA, Europe, and Asia from the natural aquatic bird reservoir through intermediate hosts including pigs and turkeys to humans. There were some remarkable parallel evolutionary developments in the swine influenza viruses in the Americas and in Eurasia. Classical swine influenza virus in the USA emerged either before or immediately after the Spanish influenza virus emerged in humans in 1918. Over the next 50 plus years this swine influenza virus became increasingly attenuated in pigs but occasionally transmitted to humans causing mild clinical infection but did not consistently spread human to human. The remarkable parallel evolution was the introduction of avian influenza virus genes independently in swine influenza viruses in Europe and the USA, with almost simultaneous acquisition of genes from seasonal human influenza. Influenza in pigs in both Eurasia and America became more aggressive necessitating the production of vaccines, and the incidence of transmission of clinical influenza to humans increased. Eventually the different triple reassortants with gene segments from avian, swine, and human influenza viruses in pigs in Europe and America met and mated and developed into the 2009 pandemic H1N1 influenza that is highly transmissible in people, pigs, and turkeys. Whether this occurred in Mexico or in Asia is currently unknown. The failure of the experts was to not recognize the importance of pigs in the evolution and host range transmission of influenza viruses with pandemic potential.

Replication of swine and human influenza viruses in juvenile and layer turkey hens

BackgroundHuman-like H3N2 influenza viruses have repeatedly been transmitted to domestic pigs in different regions of the world, but it is still uncertain whether any of these variants could become established in pig populations. The fact that different subtypes of influenza viruses have been detected in pigs makes them an ideal candidate for the genesis of a possible reassortant virus with both human and avian origins. However, the determination of whether pigs can act as a “mixing vessel” for a possible future pandemic virus is still pending an answer. This prompted us to gather the epidemiological information and investigate the genetic evolution of swine influenza viruses in Jilin, China.MethodsNasopharyngeal swabs were collected from pigs with respiratory illness in Jilin province, China from July 2007 to October 2008. All samples were screened for influenza A viruses. Three H3N2 swine influenza virus isolates were analyzed genetically and phylogenetically.ResultsInfluenza surveillance of pigs in Jilin province, China revealed that H3N2 influenza viruses were regularly detected from domestic pigs during 2007 to 2008. Phylogenetic analysis revealed that two distinguishable groups of H3N2 influenza viruses were present in pigs: the wholly contemporary human-like H3N2 viruses (represented by the Moscow/10/99-like sublineage) and double-reassortant viruses containing genes from contemporary human H3N2 viruses and avian H5 viruses, both co-circulating in pig populations.ConclusionsThe present study reports for the first time the coexistence of wholly human-like H3N2 viruses and double-reassortant viruses that have emerged in pigs in Jilin, China. It provides updated information on the role of pigs in interspecies transmission and genetic reassortment of influenza viruses.

Influenza A viruses (IAVs) pose a major public health threat due to their wide host range and pandemic potential. Pigs have been proposed as “mixing vessels” for avian, swine, and human IAVs, significantly contributing to influenza ecology. In the United States, IAVs are enzootic in commercial swine farming operations, with numerous genetic and antigenic IAV variants having emerged in the past two decades. However, the dynamics of intensive swine farming systems and their interactions with ecological factors influencing IAV evolution have not been systematically analysed. This review examines the evolution of swine IAVs in commercial farms, highlighting the role of multilevel ecological factors. A total of 61 articles published after 2000 were reviewed, with most studies conducted after 2009 in Midwestern US, followed by Southeast and South-central US. The findings reveal that ecological factors at multiple spatial scales, such as regional transportation networks, interconnectedness of swine operations, farm environments, and presence of high-density, low-genetic diversity herds, can facilitate virus transmission and enhance virus evolution. Additionally, interactions at various interfaces, such as between commercial swine and feral swine, humans, or wild birds contribute to the increase in genetic diversity of swine IAVs. The review underscores the need for comprehensive studies and improved data collection to better understand the ecological dynamics influencing swine IAV evolution. This understanding is crucial for mitigating disease burden in swine production and reducing the risk of zoonotic influenza outbreaks.

Three human influenza pandemics occurred in the twentieth century, in 1918, 1957, and 1968. Influenza pandemic strains are the results of emerging viruses from non-human reservoirs to which humans have little or no immunity. At least two of these pandemic strains, in 1957 and in 1968, were the results of reassortments between human and avian viruses. Also, many cases of swine influenza viruses have reportedly infected humans, in particular, the recent H1N1 influenza virus of swine origin, isolated in Mexico and the United States. Pigs are documented to allow productive replication of human, avian, and swine influenza viruses. Thus it has been conjectured that pigs are the “mixing vessel” that create the avian-human reassortant strains, causing the human pandemics. Hence, studying the process and patterns of viral reassortment, especially in pigs, is a key to better understanding of human influenza pandemics. In the last few years, databases containing sequences of influenza A viruses, including swine viruses, collected since 1918 from diverse geographical locations, have been developed and made publicly available. In this paper, we study an ensemble of swine influenza viruses to analyze the reassortment phenomena through several statistical techniques. The reassortment patterns in swine viruses prove to be similar to the previous results found in human viruses, both in vitro and in vivo, that the surface glycoprotein coding segments reassort most often. Moreover, we find that one of the polymerase segments (PB1), reassorted in the strains responsible for the last two human pandemics, also reassorts frequently.

Influenza A virus (IAV) can infect avian and mammalian species, including humans. The genome nature of IAVs may contribute to viral adaptation in different animal hosts, resulting in gene reassortment and the reproduction of variants with optimal fitness. As seen again in the 2009 swine-origin influenza A H1N1 pandemic, pigs are known to be susceptible to swine, avian, and human IAVs and can serve as a ‘mixing vessel’ for the generation of novel IAV variants. To this end, the emergence of swine influenza viruses must be kept under close surveillance. Herein, we report the isolation and phylogenetic study of a swine IAV, A/swine/Korea/PL01/2012 (swPL01, H3N2 subtype). After screening nasopharyngeal samples from pigs in the Gyeongsangnam-do region of Korea from December 2011 to May 2012, we isolated the swPL01 virus and sequenced its all of 8 genome segments (polymerase basic 2, PB2; polymerase basic 1, PB1; polymerase acidic, PA; hemagglutinin, HA; nucleocapsid protein, NP; neuraminidase, NA; matrix protein, M; and nonstructural protein, NS). The phylogenetic study, analyzed with reference strains registered in the National Center for Biotechnology Information (NCBI) database, indicated that the swPL01 virus was similar to the North American triple-reassortant swine strains and that the HA gene of the swPL01 virus was categorized into swine H3 cluster IV. The swPL01 virus had the M gene of the triple-reassortant swine H3N2 viruses, whereas that of other contemporary strains in Korea was transferred from the 2009 pandemic H1N1 virus. These data suggest the possibility that various swine H3N2 viruses may co-circulate in Korea, which underlines the importance of a sustained surveillance system against swine IAVs.

The pig is known as a "mixing vessel" for influenza A viruses. The co-circulation of multiple influenza A subtypes in pig populations can lead to novel reassortant strains. For this study, swine influenza surveillance was conducted from September 2011 to February 2014 on 46 swine farms in Thailand. In total, 78 swine influenza viruses were isolated from 2,821 nasal swabs, and 12 were selected for characterization by whole genome sequencing. Our results showed that the co-circulation of swine influenza subtypes H1N1, H3N2, and H1N2 in Thai swine farms was observable throughout the 3 years of surveillance. Furthermore, we repeatedly found reassortant viruses between endemic swine influenza viruses and pandemic H1N1 2009. This observation suggests that there is significant and rapid evolution of swine influenza viruses in swine. Thus, continuous surveillance is critical for monitoring novel reassortant influenza A viruses in Thai swine populations.

Infection and risk factors of human and avian influenza in pigs in south China

Swine influenza is an acute respiratory disease in pigs caused by swine influenza virus (SIV). Highly virulent SIV strains cause mortality of up to 10%. Importantly, pigs have long been considered “mixing vessels” that generate novel influenza viruses with pandemic potential, a constant threat to public health. Since its emergence in 2009 and subsequent pandemic spread, the pandemic (H1N1) 2009 (H1N1pdm) has been detected in pig farms, creating the risk of generating new reassortants and their possible infection of humans. Pathogenesis in SIV or H1N1pdm-infected pigs remains poorly characterized. Proinflammatory and antiviral cytokine responses are considered correlated with the intensity of clinical signs, and swine macrophages are found to be indispensible in effective clearance of SIV from pig lungs. In this study, we report a unique pattern of cytokine responses in swine macrophages infected with H1N1pdm. The roles of mitogen-activated protein (MAP) kinases in the regulation of the host responses were examined. We found that proinflammatory cytokines IL-6, IL-8, IL-10, and TNF-α were significantly induced and their induction was ERK1/2-dependent. IFN-β and IFN-inducible antiviral Mx and 2′5′-OAS were sharply induced, but the inductions were effectively abolished when ERK1/2 was inhibited. Induction of CCL5 (RANTES) was completely inhibited by inhibitors of ERK1/2 and JNK1/2, which appeared also to regulate FasL and TNF-α, critical for apoptosis in pig macrophages. We found that NFκB was activated in H1N1pdm-infected cells, but the activation was suppressed when ERK1/2 was inhibited, indicating there is cross-talk between MAP kinase and NFκB responses in pig macrophages. Our data suggest that MAP kinase may activate NFκB through the induction of RIG-1, which leads to the induction of IFN-β in swine macrophages. Understanding host responses and their underlying mechanisms may help identify venues for effective control of SIV and assist in prevention of future influenza pandemics.

The evolution, complexity, and diversity of swine influenza viruses in China: A hidden public health threat

Virological and serological study of human infection with swine influenza A H1N1 virus in China

Pandemic H1N1 influenza virus-like particles are immunogenic and provide protective immunity to pigs

Avian influenza: the role of the pig and public health implications

Hi Reddit, My name is Lisa Jones-Engel and I am a Senior Research Scientist at the University of Washington. For nearly two decades my research team has focused on the infectious agents that are transmitted at the increasingly porous human-primate interface in Asia. And my name is Stacey Schultz-Cherry and I am a Full Member (Professor) at St Jude Children’s Research Hospital where my research focuses on the pathogenesis of influenza virus and enteric viruses, like Astroviruses, especially in high-risk populations. My name is Erik Karlsson and I am a Postdoctoral Research Associate at St Jude Children’s Research Hospital where my research focuses on host factors, especially nutrition, that affect the pathogenesis and evolution of influenza virus and enteric viruses. My name is Christopher Small and I am the Head Data Scientist at pol.is a startup applying data visualization and machine learning to making sense of large scale conversations. I also do distributed systems and web app development consulting as ThoughtNode Software. Before all that, I worked with Erick Matsen at Fred Hutch Cancer Research Center, studying metagenomics and molecular viral epidemiology. Astroviruses are leading causes of diarrhea in children under the age of 2, immune-compromised populations and the elderly. You can get them from infected people but also through contaminated food and water. They also appear to be causing encephalitis in high-risk populations. Although we knew that Astroviruses were found in lots of different birds and animals, we never thought human viruses could infect animals or vice versa. We thought infections were species-specific (i.e. only human viruses could infect humans). That changed in 2009 when we began finding viruses in humans that were genetically more similar to animal viruses. That’s where our recent publication titled “Non-Human Primates Harbor Diverse Mammalian and Avian Astroviruses Including Those Associated with Human Infections” in PLOS Pathogens provided important new data. For the study, we sampled 879 urban, temple, captive and wild primates in Bangladesh and Cambodia. We found that 8% of primates were infected with diverse mammalian and avian Astroviruses, including those previously only known to infect humans. Clearly this exemplifies One Health and how infectious diseases of humans can impact animals we contact and potentially vice versa. We will be answering your questions about primates and Astroviruses at 1pm ET – Ask Us Anything!

Influenza A viruses of different subtypes, infect a variety of animal species and with their ability to undergo reassortments and mutations readily, are a potential public health risk. The significant carriers as well as sources of viruses are poultry birds (ducks, wild/migratory birds, chickens) and pigs, and sharing of ponds having discharged household wastewater with the excreta of humans, pigs and birds, contribute to the development of a reassortant virus through evolutionary mechanisms within ‘mixing vessels’. Pandemic threat to humans in case of bird flu is limited to 4 HA types, viz. H5, H7, H9 and H10 (AIV subtypes H5N1, H7N2, H7N3, H7N7, H7N9, H9N2, H10N8 and H10N7). Handling of infected birds or infected eggs/meat causes serious trouble in relation to transmission of bird flu rather than eating poultry products. Few authenticated cases of human-to-human transmission of avian influenza (bird flu) have been documented. However, the bird flu virus has not yet learnt the capability to be spread in a rapid and vicious manner from human-to-human in a pandemic way. This kind of human-to-human transmission of bird flu virus can trigger a human pandemic claiming millions of lives, as happened during the earlier pandemics of the twentieth century. The chance of H5N1 human pandemic virus may arise some time in the near future because of mixed infection with a bird flu (H5N1) virus and a currently circulating H3 or H1 subtype human influenza virus. If a severe pandemic occurs with a pandemic flu virus having a lethal killing weapon like that of bird flu (H5N1) virus and rapid spread like that of recent/current swine flu (H1N1) virus, then this deadly evolving influenza virus could cause serious socio-economic and public health consequences. More than 208 countries have been affected with swine flu during the last 4 years taking lives of nearly 13,600 people. Pigs act as a ‘mixing vessel’ and have played an important role in the evolution of a novel subtype of Swine flu (H1N1 subtype) virus that has enormous pandemic potential. Interestingly, transmission of swine origin influenza A viruses (H1N1, H1N2 and H3N2) can occur between humans and animals, especially in children.