Influenza A virus | |
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Structure of influenza A virus | |
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TEM micrograph of influenza A viruses | |
Virus classification ![]() | |
(unranked): | Virus |
Realm: | Riboviria |
Kingdom: | Orthornavirae |
Phylum: | Negarnaviricota |
Class: | Insthoviricetes |
Order: | Articulavirales |
Family: | Orthomyxoviridae |
Genus: | Alphainfluenzavirus |
Species: | Influenza A virus |
Influenza A virus (IAV) is a pathogen with strains that infect birds and some mammals, as well as causing seasonal flu in humans. [1] Mammals in which different strains of IAV circulate with sustained transmission are bats, pigs, horses and dogs; other mammals can occasionally become infected. [2] [3]
IAV is an enveloped negative-sense RNA virus, with a segmented genome. [3] Through a combination of mutation and genetic reassortment the virus can evolve to acquire new characteristics, enabling it to evade host immunity and occasionally to jump from one species of host to another. [4] [5]
Subtypes of IAV are defined by the combination of the antigenic H and N proteins in the viral envelope; for example, "H1N1" designates an IAV subtype that has a type-1 hemagglutinin (H) protein and a type-1 neuraminidase (N) protein. [6] Almost all possible combinations of H (1 thru 16) and N (1 thru 11) have been isolated from wild birds. [7] Further variations exist within the subtypes and can lead to very significant differences in the virus's ability to infect and cause disease, as well as to the severity of symptoms. [8] [9]
Symptoms of human seasonal flu usually include fever, cough, sore throat, muscle aches, conjunctivitis and, in severe cases, breathing problems and pneumonia that may be fatal. [10] [1] 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. [11] [12] Bird-adapted strains of the virus can be asymptomatic in some aquatic birds but lethal if they spread to other species, such as chickens. [13]
IAV disease in poultry can be can be prevented by vaccination, however biosecurity control measures are preferred. [14] [15] In humans, seasonal influenza can be treated in its early stages with antiviral medicines. [16] A global network, the Global Influenza Surveillance and Response System (GISRS) monitors the spread of influenza with the aim to inform development of both seasonal and pandemic vaccines. [17] 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 potentially zoonotic influenza viruses. IAV vaccines need to be reformulated regularly in order to keep up with changes in the virus. [18]
Influenza A virus is the only species of the genus Alphainfluenzavirus of the virus family Orthomyxoviridae . [19] There are two methods of classification, one based on surface proteins (originally serotypes), [20] and the other based on its behavior, mainly the host animal.
There are two antigenic proteins on the surface of the viral envelope, hemagglutinin and neuraminidase. [21] Different influenza virus genomes encode different hemagglutinin and neuraminidase proteins. Based on their serotype, there are 18 known types of hemagglutinin and 11 types of neuraminidase. [22] [23] 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. [22] Further variations exist within the subtypes and can lead to very significant differences in the virus's behavior. [24]
By definition, the subtyping scheme only takes into account the two outer proteins, not the at least 8 proteins internal to the virus. [25] Almost all possible combinations of H (1 thru 16) and N (1 thru 11) have been isolated from wild birds. [26] H17 and H18 have only been discovered in bats. [27]
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, [28] which describes, among other things, the subtype, year, and place of collection. Some examples include: [29]
The influenza A virus has a negative-sense, single-stranded, segmented RNA genome, enclosed in a protein 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. [30] The viral envelope comprises two main proteins; hemagglutinin (HA) and neuraminidase (NA). HA is a protein that binds the virion to host cells, enabling the RNA genetic material to invade it. Once the host cell has started manufacturing the components of new virions, NA enables the newly assembled virions to escape the host cell and go on to propagate the infection. Both proteins are antigenic; a host's immune system can react to them and produce antibodies in response. [31]
The central core of the virion contains the genetic material and the viral proteins that package and protect it. Unlike the genomes of most organisms (including humans, animals, plants, and bacteria) which are made up of double-stranded DNA, many viral genomes are made up of a different, single-stranded nucleic acid called RNA. Unusually for a virus, though, the influenza type A virus genome is not a single piece of RNA; instead, it consists of 8 segments of RNA, each piece containing either one or two genes which code for a gene product (protein). [32] The segmented nature of the genome allows for the exchange of entire genes between different viral strains. [32] [33] [31]
The predominant natural reservoir of influenza viruses is thought to be wild waterfowl. [34] The subtypes of influenza A virus are estimated to have diverged 2,000 years ago. Influenza viruses A and B are estimated to have diverged from a single ancestor around 4,000 years ago, while the ancestor of influenza viruses A and B and the ancestor of influenza virus C are estimated to have diverged from a common ancestor around 8,000 years ago. [35]
Outbreaks of influenza-like disease can be found throughout recorded history. The first probable record is by Hippocrates in 142 BCE. [36] The historian Fujikawa listed 46 epidemics of flu-like illness in Japan between 862 and 1868. [37] In Europe and the Americas, a number of epidemics were recorded through the Middle Ages and up to the end of the 19th century. [36]
In 1918-1919 came the first flu pandemic of the 20th century, known generally as the " Spanish flu ", which caused an estimated 20 to 50 million deaths worldwide. It is now known that this was caused by an immunologically novel H1N1 subtype of influenza A. [38] The next pandemic took place in 1957, the " Asian flu ", which was caused by a H2N2 subtype of the virus in which the genome segments coding for HA and NA appeared to have derived from avian influenza strains by reassortment, while the remainder of the genome was descended from the 1918 virus. [39] The 1968 pandemic (" Hong Kong flu") was caused by a H3N2 subtype in which the NA segment was derived from the 1957 virus, while the HA segment had been reassorted from an avian strain of influenza. [39]
In the 21st century, a strain of H1N1 flu (since titled H1N1pdm09 ) which was antigenically very different from previous H1N1 strains, leading to a pandemic in 2009. Because of its close resemblance to some strains circulating in pigs, this became known as " Swine flu " [40]
Influenza A virus continues to circulate and evolve in birds and pigs. Almost all possible combinations of H (1 thru 16) and N (1 thru 11) have been isolated from wild birds. [26] As of June 2024, two particularly virulent IAV strains - H5N1 and H7N9 - are predominant in wild bird populations. These frequently cause outbreaks in domestic poultry, with occasional spillover infections in humans who are in close contact with poultry. [41] [42]
Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. [43] The segmentation of the influenza A virus genome facilitates genetic recombination by segment reassortment in hosts who become infected with two different strains of influenza viruses at the same time. [44] [45] With reassortment between strains, an avian strain which does not affect humans may acquire characteristics from a different strain which enable it to infect and pass between humans - a zoonotic event. [46] It is thought that all influenza A viruses causing outbreaks or pandemics among humans since the 1900s originated from strains circulating in wild aquatic birds through reassortment with other influenza strains. [47] [48] It is possible (though not certain) that pigs may act as an intermediate host for reassortment. [49]
The Global Influenza Surveillance and Response System (GISRS) is a global network of laboratories that monitor the spread of influenza with the aim to provide the World Health Organization with influenza control information and to inform vaccine development. [50] Several millions of specimens are tested by the GISRS network annually through a network of laboratories in 127 countries. [51] As well as human viruses, GISRS monitors avian, swine, and other potentially zoonotic influenza viruses.
Flu season is an annually recurring time period characterized by the prevalence of an outbreak of influenza, caused either by Influenza A or by Influenza B. The season occurs during the cold half of the year in temperate regions; November through February in the northern hemisphere and May to October in the southern hemisphere. Flu seasons also exist in the tropics and subtropics, with variability from region to region. [53] Annually, about 3 to 5 million cases of severe illness and 290,000 to 650,000 deaths from seasonal flu occur worldwide. [1]
There are several possible reasons for the winter peak in temperate regions:
A zoonosis a disease in a human caused by a pathogen (such as a bacterium, or virus) that has jumped from a non-human to a human. [56] [57] Avian and pig influenza viruses can, on rare occasions, transmit to humans and cause zoonotic influenza virus infections; these infections are usually confined to people who have been in close contact with infected animals or material such as infected feces and meat, they do not spread to other humans. Symptoms of these infections in humans vary greatly; some are in asymptomatic or mild while others can cause severe disease, leading to severe pneumonia and death. [58] A wide range of Influenza A virus subtypes have been found to cause zoonotic disease. [58] [59]
Zoonotic infections can be prevented by good hygiene, by preventing farmed animals from coming into contact with wild animals, and by using appropriate personal protective equipment. [57]
As of June 2024, there is concern about two subtypes of avian influenza which are circulating in wild bird populations worldwide, H5N1 and H7N9. Both of these have potential to devastate poultry stocks, and both have jumped to humans with relatively high case fatality rates. [59] H5N1 in particular has infected a wide range of mammals and may be adapting to mammalian hosts. [60]
As of June 2024, the influenza viruses which circulate widely in humans are IAV subtypes H1N1 and H2N3, together with Influenza B. [61] Annual vaccination is the primary and most effective way to prevent influenza and influenza-associated complications, especially for high-risk groups. [62] Vaccines against the flu are trivalent or quadrivalent, providing protection against the dominant strains of IAV(H1N1) and IAV(H3N2), and one or two influenza B virus strains; the formulation is continually reviewed in order to match the predominant strains in circulation. [63] [64]
Poultry and other animals - it is possible to vaccinate poultry and pigs against specific strains of influenza. Vaccination should be combined with other control measures such as infection monitoring, early detection and biosecurity. [65] [66] [67]
The main treatment for mild influenza is supportive; rest, fluids, and over-the-counter medicines to alleviate symptoms while the body's own immune system works to recover from infection. Antiviral drugs are recommended for those with severe symptoms, or for those who are at risk of developing complications such as pneumonia. [68] [1]
The symptoms of influenza are similar to those of a cold, although usually more severe and less likely to include a runny nose. [72] The onset of symptoms is sudden, and initial symptoms are predominately non-specific: a sudden fever; muscle aches; cough; fatigue; sore throat; headache; difficulty sleeping; loss of appetite; diarrhoea or abdominal pain; nausea and vomiting. [73]
Some species of wild aquatic birds act as natural asymptomatic carriers of a large variety of influenza A viruses. [74] Symptoms of avian influenza vary according to both the strain of virus underlying the infection, and on the species of bird affected. Symptoms of influenza in wild birds may include swollen head, watery eyes, unresponsiveness, lack of coordination, respiratory distress such as sneezing or gurgling. [75]
Because of the impact of avian influenza on economically important chicken farms, avian virus strains are classified as either highly pathogenic (and therefore potentially requiring vigorous control measures) or low pathogenic. The test for this is based solely on the effect on chickens - a virus strain is highly pathogenic avian influenza (HPAI) if 75% or more of chickens die after being deliberately infected with it, or if it is genetically similar to such a strain. The alternative classification is low pathogenic avian influenza (LPAI). [76] Classification of a virus strain as either LPAI or HPAI is based on the severity of symptoms in domestic chickens and does not predict severity of symptoms in other species. Chickens infected with LPAI display mild symptoms or are asymptomatic, whereas HPAI causes serious breathing difficulties, significant drop in egg production, and sudden death. [77]
Signs of swine flu in pigs can include fever, depression, coughing (barking), discharge from the nose or eyes, sneezing, breathing difficulties, eye redness or inflammation, and going off feed. Some pigs infected with influenza, however, may show no signs of illness at all. Swine flu subtypes are principally H1N1, H1N2, and H3N2; [78] it is spread either through close contact between animals or by the movement of contaminated equipment between farms. [79] Humans who are in close contact with pigs can sometimes become infected. [80]
Equine influenza can affect horses, donkeys, and mules; [81] it has a very high rate of transmission among horses, and a relatively short incubation time of one to three days. [82] Clinical signs of equine influenza include fever, nasal discharge, have a dry, hacking cough, depression, loss of appetite and weakness. [82] EI is caused by two subtypes of influenza A viruses: H7N7 and H3N8, which have evolved from avian influenza A viruses. [83]
Most animals infected with canine influenza A will show symptoms such as coughing, runny nose, fever, lethargy, eye discharge, and a reduced appetite lasting anywhere from 2–3 weeks. [84] There are two different influenza A dog flu viruses: one is an H3N8 virus and the other is an H3N2 virus. [84] The H3N8 strain has evolved from an equine influenza avian virus which has adapted to sustained transmission among dogs. The H3N2 strain is derived from an avian influenza which jumped to dogs in 2004 in either Korea or China. [84] It is likely that the virus persists in both animal shelters and kennels, as well as in farms where dogs are raised for meat production. [85]
The first bat flu virus, IAV(H17N10), was first discovered in 2009 in little yellow-shouldered bats (Sturnira lilium) in Guatemala. [86] In 2012 a second bat influenza A virus IAV(H18N11) was discovered in flat-faced fruit-eating bats (Artibeus planirostris) from Peru. [87] [88] [89] Bat influenza viruses have been found to be poorly adapted to non-bat species. [90]
FI6, an antibody that targets the hemagglutinin protein, was discovered in 2011. FI6 is the only known antibody effective against all 16 subtypes of the influenza A virus. [91] [92] [93]
Avian influenza, also known as avian flu or bird flu, is a disease caused by the influenza A virus (IAV) which primarily affects birds but can sometimes affect mammals including humans. Wild aquatic birds are the primary host of Influenza A virus (IAV), which is endemic in many bird populations.
Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains. The term is often applied specifically to influenza, as that is the best-known example, but the process is also known to occur with other viruses, such as visna virus in sheep. Antigenic shift is a specific case of reassortment or viral shift that confers a phenotypic change.
Orthomyxoviridae is a family of negative-sense RNA viruses. It includes seven genera: Alphainfluenzavirus, Betainfluenzavirus, Gammainfluenzavirus, Deltainfluenzavirus, Isavirus, Thogotovirus, and Quaranjavirus. The first four genera contain viruses that cause influenza in birds and mammals, including humans. Isaviruses infect salmon; the thogotoviruses are arboviruses, infecting vertebrates and invertebrates. The Quaranjaviruses are also arboviruses, infecting vertebrates (birds) and invertebrates (arthropods).
Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus, which causes influenza (flu), predominantly in birds. It is enzootic in many bird populations, and also panzootic. A/H5N1 virus can also infect mammals that have been exposed to infected birds; in these cases, symptoms are frequently severe or fatal.
Swine influenza is an infection caused by any of several types of swine influenza viruses. Swine influenza virus (SIV) or swine-origin influenza virus (S-OIV) refers to any strain of the influenza family of viruses that is endemic in pigs. As of 2009, identified SIV strains include influenza C and the subtypes of influenza A known as H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3.
In virology, influenza A virus subtype H1N1 (A/H1N1) is a subtype of influenza A virus. Major outbreaks of H1N1 strains in humans include the 1918 Spanish flu pandemic, the 1977 Russian flu pandemic and the 2009 swine flu pandemic. It is an orthomyxovirus that contains the glycoproteins hemagglutinin (H) and neuraminidase (N), antigens whose subtypes are used to classify the strains of the virus as H1N1, H1N2 etc. Hemagglutinin causes red blood cells to clump together and binds the virus to the infected cell. Neuraminidase is a type of glycoside hydrolase enzyme which helps to move the virus particles through the infected cell and assist in budding from the host cells.
An influenza pandemic is an epidemic of an influenza virus that spreads across a large region and infects a large proportion of the population. There have been six major influenza epidemics in the last 140 years, with the 1918 flu pandemic being the most severe; this is estimated to have been responsible for the deaths of 50–100 million people. The 2009 swine flu pandemic resulted in under 300,000 deaths and is considered relatively mild. These pandemics occur irregularly.
Influenza A virus subtype H3N2 (A/H3N2) is a subtype of viruses that causes influenza (flu). H3N2 viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. In years in which H3N2 is the predominant strain, there are more hospitalizations.
The global spread of H5N1 influenza in birds is considered a significant pandemic threat. While other H5N1 influenza strains are known, they are significantly different on a genetic level from a highly pathogenic, emergent strain of H5N1, which was able to achieve hitherto unprecedented global spread in 2008. The H5N1 strain is a fast-mutating, highly pathogenic avian influenza virus (HPAI) found in multiple bird species. It is both epizootic and panzootic. Unless otherwise indicated, "H5N1" in this timeline refers to the 2008 highly pathogenic strain of H5N1.
Transmission and infection of H5N1 from infected avian sources to humans has been a concern since the first documented case of human infection in 1997, due to the global spread of H5N1 that constitutes a pandemic threat.
Influenza B virus is the only species in the genus Betainfluenzavirus in the virus family Orthomyxoviridae.
Influenza A virus subtype H1N2 (A/H1N2) is a subtype of the species Influenza A virus. It is currently endemic in pig populations and is occasionally seen in humans.
H5N1 genetic structure is the molecular structure of the H5N1 virus's RNA.
Spanish flu research concerns studies regarding the causes and characteristics of the Spanish flu, a variety of influenza that in 1918 was responsible for the worst influenza pandemic in modern history. Many theories about the origins and progress of the Spanish flu persisted in the literature, but it was not until 2005, when various samples of lung tissue were recovered from American World War I soldiers and from an Inupiat woman buried in permafrost in a mass grave in Brevig Mission, Alaska, that significant genetic research was made possible.
H5N1 influenza virus is a type of influenza A virus which mostly infects birds. H5N1 flu is a concern due to the its global spread that may constitute a pandemic threat. The yardstick for human mortality from H5N1 is the case-fatality rate (CFR); the ratio of the number of confirmed human deaths resulting from infection of H5N1 to the number of those confirmed cases of infection with the virus. For example, if there are 100 confirmed cases of a disease and 50 die as a consequence, then the CFR is 50%. The case fatality rate does not take into account cases of a disease which are unconfirmed or undiagnosed, perhaps because symptoms were mild and unremarkable or because of a lack of diagnostic facilities. The Infection Fatality Rate (IFR) is adjusted to allow for undiagnosed cases.
Influenza, commonly known as "the flu" or just "flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms begin one to four days after exposure to the virus and last for about two to eight days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia from the virus or a subsequent bacterial infection. Other complications include acute respiratory distress syndrome, meningitis, encephalitis, and worsening of pre-existing health problems such as asthma and cardiovascular disease.
The 2009 swine flu pandemic, caused by the H1N1/swine flu/influenza virus and declared by the World Health Organization (WHO) from June 2009 to August 2010, was the third recent flu pandemic involving the H1N1 virus. The first identified human case was in La Gloria, Mexico, a rural town in Veracruz. The virus appeared to be a new strain of H1N1 that resulted from a previous triple reassortment of bird, swine, and human flu viruses which further combined with a Eurasian pig flu virus, leading to the term "swine flu".
The pandemic H1N1/09 virus is a swine origin influenza A virus subtype H1N1 strain that was responsible for the 2009 swine flu pandemic. This strain is often called swine flu by the public media due to the prevailing belief that it originated in pigs. The virus is believed to have originated around September 2008 in central Mexico.
The FluChip is a low-density DNA microarray for the identification of influenza viruses, originally developed at the University of Colorado at Boulder in the laboratory of Professor Kathy Rowlen in collaboration with the Centers for Disease Control and Prevention (CDC) in Atlanta.
Type A influenza vaccine is for the prevention of infection of influenza A virus and also the influenza-related complications. Different monovalent type A influenza vaccines have been developed for different subtypes of influenza A virus including H1N1 and H5N1. Both intramuscular injection or intranasal spray are available on market. Unlike the seasonal influenza vaccines which are used annually, they are usually used during the outbreak of certain strand of subtypes of influenza A. Common adverse effects includes injection site reaction and local tenderness. Incidences of headache and myalgia were also reported with H1N1 whereas cases of fever has also been demonstrated with H5N1 vaccines. It is stated that immunosuppressant therapies would reduce the therapeutic effects of vaccines and that people with egg allergy should go for the egg-free preparations.
This Memorandum was drafted by the signatories listed on page 590 on the occasion of a meeting held in Geneva in February 1980.
Highly pathogenic avian influenza virus is on every top ten list available for potential agricultural bioweapon agents