The Drivers of Pathology in Zoonotic Avian Influenza: The Interplay Between Host and Pathogen

Abstract

The emergence of zoonotic strains of avian influenza (AI) that cause high rates of mortality in people has caused significant global concern, with a looming threat that one of these strains may develop sustained human-to-human transmission and cause a pandemic outbreak. Most notable of these viral strains are the H5N1 highly pathogenic AI and the H7N9 low pathogenicity AI viruses, both of which have mortality rates above 30%. Understanding of their mechanisms of infection and pathobiology is key to our preparation for these and future viral strains of high consequence. AI viruses typically circulate in wild bird populations, commonly infecting waterfowl and also regularly entering commercial poultry flocks. Live poultry markets provide an ideal environment for the spread AI and potentially the selection of mutants with a greater propensity for infecting humans because of the potential for spill over from birds to humans. Pathology from these AI virus infections is associated with a dysregulated immune response, which is characterized by systemic spread of the virus, lymphopenia, and hypercytokinemia. It has been well documented that host/pathogen interactions, particularly molecules of the immune system, play a significant role in both disease susceptibility as well as disease outcome. Here, we review the immune/virus interactions in both avian and mammalian species, and provide an overview or our understanding of how immune dysregulation is driven. Understanding these susceptibility factors is critical for the development of new vaccines and therapeutics to combat the next pandemic influenza.

Identification of lncRNA‐155 encoded by MIR155HG as a novel regulator of innate immunity against influenza A virus infection

“…Coinfection of a particular host can give rise to genetically different population of influenza virus via de novo mutations and genetic reassortment (Lyons & Lauring, 2018;Nelson & Holmes, 2007;Schmolke & Garcia-Sastre, 2010). Moreover, the transmission of newly emerged IAV from animals to humans can lead to high unanticipated mortalities (~35-50%; Horman, Nguyen, Kedzierska, Bean, & Layton, 2018). Moreover, the transmission of newly emerged IAV from animals to humans can lead to high unanticipated mortalities (~35-50%; Horman, Nguyen, Kedzierska, Bean, & Layton, 2018).…”

“…This unique IAV evolution style makes the annually local formulated vaccines be variably effective (Pica & Palese, 2013) and leads to the emergence of drug-resistant strains, rendering some of the available anti-influenza virus drugs to be ineffective over time (Hurt, 2014). Moreover, the transmission of newly emerged IAV from animals to humans can lead to high unanticipated mortalities (~35-50%; Horman, Nguyen, Kedzierska, Bean, & Layton, 2018). Therefore, better understanding of IAV-host interaction is required for the control of this disease, and there is an undeniable need to identify the immune factors working against influenza virus for the development of sustainable and effective anti-influenza strategies.…”

Characterization and Phylodynamics of Reassortant H12Nx Viruses in Northern Eurasia

“…The data and results presented here further our knowledge of the ecology of rare AIV subtypes. Additionally, we performed a pathogenic risk assessment of these variants regarding their potential threat to humans [10,11].…”

Prevention of Highly Pathogenic Avian Influenza A/H5N1 Infection by Passive Immunotherapy Using Antiserum

“…Avian influenza is most often spread by contact between infected and healthy birds, although it can also be spread indirectly through contaminated equipment [1] [2] [3]. Highly pathogenic strains of avian influenza viruses transmit imme-diately among birds and can destroy a flock within one day.…”