The influenza A virus is known to cause influenza in birds and some mammals, like humans. Different subtypes of the influenza A virus have been isolated from wild birds. Some subtypes of the influenza A virus can cause severe symptoms both in domestic poultry and (rarely) in humans and can even lead to death. Occasionally, viruses can be transmitted from wild birds to domestic animals, like chickens or pigs. This may give rise to human influenza . <ref name="Arti2">Transmission of Avian Influenza A Viruses Between Animals and People, CDC, 2015, https://www.cdc.gov/flu/avianflu/virus-transmission.htm</ref>.

Influenza A viruses are negative-sense, single-stranded RNA viruses. Different subtypes of influenza A exist, these are characterized by proteins on the outermost membrane of the virus, called hemagglutinin (H or HA) and neuraminidase (N or NA). H and N are the antigens of the virus, and play an important role in the interaction between the host’s immunological response and the virus. Recently, researchers have reported the discovery of an antibody which is generally effective against all subtypes of the influenza A virus.<ref name="Arti3">Super antibody' fights off flu, BBC, 2011, James Gallagher, https://www.bbc.com/news/health-14324901</ref>.

The subtype which will be used in SensUs 2021 is H1N1. Historically, H1N1 has been responsible for most deaths due to influenza. It is a popular influenza strain for research purposes.<ref name="Arti4">Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection, Research Gate, 2020, Sun, Honglei & Xiao, Yihong & Liu, Jiyu & Wang, Dayan & Li, Fangtao & Wang, Chenxi & Li, Chong & Zhu, Junda & Song, Jingwei & Sun, Haoran & Zhimin, Jiang & Liu, Litao & Zhang, Xin & Wei, Kai & Dongjun, Hou & Pu, Juan & Sun, Yipeng & Tong, Qi & Bi, Yuhai & Liu, Jinhua https://www.researchgate.net/publication/342555087_Prevalent_Eurasian_avian-like_H1N1_swine_influenza_virus_with_2009_pandemic_viral_genes_facilitating_human_infection</ref><ref name="Arti5">Comparison of Hospitalized Patients With ARDS Caused by COVID-19 and H1N1, CHEST, Xiao Tang, Rong-Hui Du, Rui Wang, Tan-Ze Cao, Lu-Lu Guan, Cheng-Qing Yang, Qi Zhu, Ming Hu, Xu-Yan Li, Ying Li, Li-Rong Liang, Zhao-Hui Tong, Bing Sun, Peng Peng, Huan-Zhong Shi, 2020, https://www.sciencedirect.com/science/article/pii/S0012369220305584</ref><ref name="Arti6">Landscape of coordinated immune responses to H1N1 challenge in humans, Journal of Clinical Investigation, 2020, Zainab Rahil, Rebecca Leylek, Christian M. Schürch, Han Chen, Zach Bjornson-Hooper, Shannon R. Christensen, Pier Federico Gherardini, Salil S. Bhate, Matthew H. Spitzer, Gabriela K. Fragiadakis, Nilanjan Mukherjee, Nelson Kim, Sizun Jiang, Jennifer Yo, Brice Gaudilliere, Melton Affrime, Bonnie Bock, Scott E. Hensley, Juliana Idoyaga, Nima Aghaeepour, Kenneth Kim, Garry P. Nolan, David R. McIlwain https://www.sciencedirect.com/science/article/pii/S0012369220305584</ref>. Due to its popularity among researchers, antigens and antibodies are commercially available, making H1N1 suitable as a target for the SensUs competition.Influenza A vaccines for humans have been developed. New versions of the vaccines are developed twice per year for use all over the world, which is necessary due to rapid mutations of the influenza virus. Every year during flu season, a large part of the population is vaccinated in order to protect individuals against the virus. However, due to unforeseen mutations of the virus, it might be possible that in a certain year a vaccine will prove ineffective. In that case large portions of the population would be at risk and a pandemic could occur. The probability of a major influenza A pandemic is estimated to be around 0.5-1% . each year<ref name="Arti7">Pandemic risk: how large are the expected losses?, WHO, 2017, Victoria Y Fan, Dean T Jamisonb & Lawrence H Summers, https://www.who.int/bulletin/volumes/96/2/17-199588.pdf</ref>.

A lack of data up until 1500 AC complicates the research on influenza before that period.<ref name="Arti8">Internet‐Based Intelligence in Public Health Emergencies, NATO Science for Peace and Security Series - E: Human and Societal Dynamics, 2013 Mordini E., Green M., https://www.iospress.nl/book/internet%E2%80%90based-intelligence-in-public-health-emergencies/</ref>. Possibly the first influenza pandemic occurred around 6000 BC in China. The symptoms of human influenza seem to have been clearly described by Hippocrates, roughly 2,400 years ago<ref name="Arti9">2,500-year Evolution of the Term Epidemic, Emerging infectious diseases, 2006, Martin PM, Martin-Granel E, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373038/</ref>. Although the virus seems to have caused epidemics throughout human history, historical data on influenza is difficult to interpret, due to the fact that symptoms of influenza are similar to those found in other respiratory diseases, like RSV (respiratory syncytial virus).

The most infamous and lethal outbreak was the 1918 flu pandemic (Spanish flu) (type A influenza, H1N1 subtype), which lasted into 1920. The number of deaths is unknown, but estimates range from 17 to 100 million people.<ref name="Arti10">Reassessing the Global Mortality Burden of the 1918 Influenza Pandemic, American journal of epidemiology, 2018, Spreeuwenberg P, Kroneman M, Paget J, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314216/</ref>. This pandemic has been described as "the greatest medical holocaust in history"<ref name="Arti11">Reviewing the History of Pandemic Influenza: Understanding Patterns of Emergence and Transmission

One of the most recent outbreaks of influenza was the 2009 Swine Flu. Similar to the Spanish Flu, it was also of the subtype H1N1. The death toll of the 2009 pandemic is estimated to be around 150,000 to 575,000.<ref name="Arti12">2009 H1N1 Pandemic (H1N1pdm09 virus), centers for disease control and prevention, 2010, https://www.cdc.gov/flu/pandemic-resources/2009-h1n1-pandemic.html</ref>.

The virus particle (virion) is 80–120 nanometers in diameter.<ref name="Arti13">Native Morphology of Influenza Virions, Frontiers in microbiology, 2011, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249889/</ref>. The virion shape can be spherical, elliptical, or even filamentous with a length of tens of micrometers<ref name="Arti13">Native Morphology of Influenza Virions, Frontiers in microbiology, 2011, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249889/</ref>. The virion is made up of a viral envelope containing two main types of proteins, wrapped around a central core. The two large proteins found on the outside of viral particles are hemagglutinin (HA) and neuraminidase (NA). HA is a protein that mediates binding of the virion to target cells and entry of the viral genome into the target cell, and therefore plays an important role in infecting healthy cells. NA is involved in releasing the progeny viruses once a cell has been infected and has started producing the virus itself.<ref name="Arti14">Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase, Virology journal , 2013, Cohen M, Zhang XQ, Senaati HP, Chen HW, Varki NM, Schooley RT, Gagneux P, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842836/</ref>.

These two proteins are a target of interest for antiviral drugs.<ref name="Arti15">Recent Strategies in the Search for New Anti-Influenza Therapies, Current Drug Targets , 2003, J.C. Wilson, M. von Itzstein, https://www.eurekaselect.com/63785/article</ref>. Furthermore, they are also the antigen proteins to which a host antibodies can bind and trigger an immune response. Influenza type A viruses are categorized into different subtypes, or strains, based on which type of these two proteins is present on the surface of the virion. Currently, there are 16 subtypes of HA and 9 subtypes of NA known to exist. The most prevalent form of the different subtypes is H1N1. Single hemagglutinin-neuraminidase proteins, in which both HA and NA are found in a single protein, also exist. However, these will not be used in SensUs 2021.