Influenza A virus, or IAV, is a pathogen with strains that cause seasonal flu in humans; it can also infect birds and some mammals. Strains of IAV circulate constantly in bats, pigs, horses, and dogs, while other mammals may be infected occasionally. It has also been the cause of a number of pandemics, most notably the Spanish Flu pandemic from 1918–1920. Subtypes of IAV are defined by the combination of the molecules on the surface of the virus which provoke an immune response; for example, "H1N1" denotes a subtype that has a type-1 hemagglutinin (H) protein and a type-1 neuraminidase (N) protein. Variations within subtypes affect how easily the virus spreads, the severity of illness, and its ability to infect different hosts. The virus changes through mutation and genetic reassortment, allowing it to evade immunity and sometimes jump between species. Symptoms of human seasonal flu usually include fever, cough, sore throat, muscle aches and, in severe cases, breathing problems and pneumonia that may be fatal. Humans can rarely become infected with strains of avian or swine influenza, usually as a result of close contact with infected animals; symptoms range from mild to severe including death. Bird-adapted strains of the virus can be asymptomatic in some aquatic birds but lethal if they spread to other species, such as chickens. IAV disease in poultry can be prevented by vaccination; however, biosecurity control measures such as quarantine, segregation, and good hygiene are preferred. In humans, seasonal influenza can be prevented by vaccination, or treated in its early stages with antiviral medicines. The Global Influenza Surveillance and Response System (GISRS) monitors the spread of influenza worldwide and informs development of both seasonal and pandemic vaccines. Several millions of specimens are tested by the GISRS network annually through a network of laboratories in 127 countries. As well as human viruses, GISRS monitors avian, swine, and other influenza viruses which could potentially infect humans. IAV vaccines need to be reformulated regularly in order to keep up with changes in the virus.
Virology
Taxonomy Influenza A virus, or IAV (scientific name Alphainfluenzavirus influenzae), is the only species of the genus Alphainfluenzavirus of the virus family Orthomyxoviridae.
Classification There are two methods of classification, one based on the antigenic surface proteins, and the other based on its behavior, mainly the host animal.
Subtypes There are two antigenic proteins on the surface of the viral envelope, hemagglutinin and neuraminidase. Based on their serotype, there are 18 known types of hemagglutinin and 11 types of neuraminidase. Subtypes of IAV are classified by their combination of H and N proteins. For example, "H5N1" designates an influenza A subtype that has a type-5 hemagglutinin (H) protein and a type-1 neuraminidase (N) protein. By definition, the subtyping scheme only takes into account the two outer proteins, not the additional eight or more proteins which are coded by the genome. Almost all possible combinations of H (1 through 16) and N (1 through 11) have been isolated from wild birds. H17 and H18 have only been discovered in bats. Further variation exists within viral subtypes which may lead to significant differences in behavior.
Influenza virus nomenclature Due to the high variability of the virus, subtyping is not sufficient to uniquely identify a strain of influenza A virus. To unambiguously describe a specific isolate of virus, researchers use the Influenza virus nomenclature, which describes, among other things, the subtype, year, and place of collection. Some examples include:
A/Rio de Janeiro/62434/2021 (H3N2). The starting A indicates that the virus is an influenza A virus. Rio de Janeiro indicates the place of collection. 62434 is a laboratory sequence number. 2021 (or just 21) indicates that the sample was collected in 2021. No species is mentioned so by default, the sample was collected from a human. (H3N2) indicates the subtype of the virus. A/swine/South Dakota/152B/2009 (H1N2). This example shows an additional field before the place: swine. It indicates that the sample was collected from a pig. A/California/04/2009 A(H1N1)pdm09. This example carries an unusual designation in the last part: instead of a usual (H1N1), it uses A(H1N1)pdm09. This was in order to distinguish the Pandemic H1N1/09 virus lineage from older H1N1 viruses.
Structure and genetics
Structure
The influenza A virus has a negative-sense, single-stranded, segmented RNA genome, enclosed in a lipid envelope. The virus particle (also called the "virion") is 80–120 nanometers in diameter, such that the smallest virions adopt an elliptical shape; larger virions have a filamentous shape. Core – The central core of the virion contains the viral RNA genome, which is made of eight separate segments. The nucleoprotein (NP) coats the viral RNA to form a ribonucleoprotein that assumes a helical (spiral) configuration. Three large proteins (PB1, PB2, and PA), which are responsible for RNA transcription and replication, are bound to each segment of viral RNP. Capsid – The matrix protein M1 forms a layer between the nucleoprotein and the envelope, called the capsid. Envelope – The viral envelope consists of a lipid bilayer derived from the host cell. Two viral proteins; hemagglutinin (HA) and neuraminidase (NA), are inserted into the envelope and are exposed as spikes on the surface of the virion. Both proteins are antigenic; a host's immune system can react to them and produce antibodies in response. The M2 protein forms an ion channel in the envelope and is responsible for uncoating the virion once it has bound to a host cell.
Genome The table below presents a concise summary of the influenza genome and the principal functions of the proteins which are encoded. Segments are conventionally numbered from 1 to 8 in descending order of length.
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