NIAID illustration of potential influenza genetic reassortment
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.[1] Antigenic shift is a specific case of reassortment or viral shift that confers a phenotypic change.
Antigenic shift is contrasted with antigenic drift, which is the natural mutation over time of known strains of influenza (or other things, in a more general sense) which may lead to a loss of immunity, or in vaccine mismatch. Antigenic drift occurs in all types of influenza including influenza A, influenza B and influenza C. Antigenic shift, however, occurs only in influenza A because it infects more than just humans.[2] Affected species include other mammals and birds, giving influenza A the opportunity for a major reorganization of surface antigens. Influenza B and C principally infect humans, minimizing the chance that a reassortment will change its phenotype drastically.[3]
In 1940s, Maurice Hilleman discovered antigenic shift, which is important for the emergence of new viral pathogens as it is a pathway that viruses may follow to enter a new niche.[4][5]
Role in the transmission of influenza viruses from non-human animals to people
Influenza A viruses are found in many different animals, including ducks, chickens, pigs, humans, whales, horses, and seals.[3] Influenza B viruses circulate widely principally among humans, though it has recently been found in seals.[6] Flu strains are named after their types of hemagglutinin and neuraminidase surface proteins (of which there are 18 and 9 respectively), so they will be called, for example, H3N2 for type-3 hemagglutinin and type-2 neuraminidase. Some strains of avian influenza (from which all other strains of influenza A are believed to stem[2]) can infect pigs or other mammalian hosts. When two different strains of influenza infect the same cell simultaneously, their protein capsids and lipid envelopes are removed, exposing their RNA, which is then transcribed to mRNA. The host cell then forms new viruses that combine their antigens; for example, H3N2 and H5N1 can form H5N2 this way. Because the human immune system has difficulty recognizing the new influenza strain, it may be highly dangerous, and result in a new pandemic.[3]
Influenza viruses which have undergone antigenic shift have caused the Asian Flu pandemic of 1957, the Hong Kong Flu pandemic of 1968, and the Swine Flu scare of 1976. Until recently, such combinations were believed to have caused the infamous Spanish flu outbreak of 1918 which killed 40~100 million people worldwide. However, more recent research suggests the 1918 pandemic was caused by the antigenic drift of a fully avian virus to a form that could infect humans efficiently.[7][8] The most recent 2009 H1N1 outbreak was a result of antigenic shift and reassortment between human, avian, and swine viruses.[9]
Role of pigs in Influenza antigenic shift
Pigs are especially important in antigenic shift of influenza viruses. Because pigs can be infected with strains of influenza that infect various other species of animals, they act as 'mixing pots' for the virus. When multiple virus strains, such as a duck and human influenza strain, infect the same pig, antigenic shift is likely to occur. While most of the virus strains resulting from this will be dead-end strains, a few have the potential to become pandemic viruses.[10]
Influenza A virus (IAV) is a pathogen that causes the flu in birds and some mammals, including humans. It is an RNA virus whose subtypes have been isolated from wild birds. Occasionally, it is transmitted from wild to domestic birds, and this may cause severe disease, outbreaks, or human influenza pandemics.
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).
Antigenic drift is a kind of genetic variation in viruses, arising from the accumulation of mutations in the virus genes that code for virus-surface proteins that host antibodies recognize. This results in a new strain of virus particles that is not effectively inhibited by the antibodies that prevented infection by previous strains. This makes it easier for the changed virus to spread throughout a partially immune population. Antigenic drift occurs in both influenza A and influenza B viruses.
Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus which can cause illness in humans and many other species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for highly pathogenic avian influenza virus of type A of subtype H5N1, is the highly pathogenic causative agent of H5N1 flu, commonly known as avian influenza. It is enzootic in many bird populations, especially in Southeast Asia. One strain of HPAI A(H5N1) is spreading globally after first appearing in Asia. It is epizootic and panzootic, killing tens of millions of birds and spurring the culling of hundreds of millions of others to stem its spread. Many references to "bird flu" and H5N1 in the popular media refer to this strain.
The Hong Kong flu, also known as the 1968 flu pandemic, was a flu pandemic whose outbreak in 1968 and 1969 killed between one and four million people globally. It is among the deadliest pandemics in history, and was caused by an H3N2 strain of the influenza A virus. The virus was descended from H2N2 through antigenic shift, a genetic process in which genes from multiple subtypes are reassorted to form a new virus.
Reassortment is the mixing of the genetic material of a species into new combinations in different individuals. Several different processes contribute to reassortment, including assortment of chromosomes, and chromosomal crossover. It is particularly used when two similar viruses that are infecting the same cell exchange genetic material. In particular, reassortment occurs among influenza viruses, whose genomes consist of eight distinct segments of RNA. These segments act like mini-chromosomes, and each time a flu virus is assembled, it requires one copy of each segment.
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 most recent, the 2009 swine flu pandemic, resulted in under 300,000 deaths and is considered relatively mild. These pandemics occur irregularly.
Influenza A virus subtype H2N2 (A/H2N2) is a subtype of Influenza A virus. H2N2 has mutated into various strains including the "Asian flu" strain, H3N2, and various strains found in birds. It is also suspected of causing a human pandemic in 1889. The geographic spreading of the 1889 Russian flu has been studied and published.
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.
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.
Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype of the Influenza A virus or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus. These strains are named after Fujian, a coastal province in Southeast China.
Influenza, commonly known as "the 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 from one to four days after exposure to the virus and last for about 2–8 days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia, which can be caused by the virus or by a subsequent bacterial infection. Other complications of infection 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, is the third recent flu pandemic involving the H1N1 virus. The first two cases were discovered independently in the United States in April 2009. 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. For other names, see the Nomenclature section below.
A universal flu vaccine is a flu vaccine that is effective against all influenza strains regardless of the virus sub type, antigenic drift or antigenic shift. Hence it should not require modification from year to year. As of 2021 no universal flu vaccine had been approved for general use, several were in development, and one was in clinical trial.
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