influenza influenza 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 (typically two days) 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. for other uses, see influenza (disambiguation), flu (disambiguation), and grippe (disambiguation). "flus" redirects here. for the diagnostic class of thyroid nodules, see flus. influenzaother namesflu, the flu, grippeinfluenza virus, magnified approximately 100,000 timesspecialtyinfectious diseasesymptomsfever, runny nose, sore throat, muscle pain, headache, coughing, fatigueusual onset1–4 days after exposureduration2–8 dayscausesinfluenza virusespreventionhand washing, flu vaccinesmedicationantiviral drugs such as oseltamivirfrequency3–5 million severe cases per yeardeaths>290,000–650,000 deaths per year there are four types of influenza virus: a, b, c, and d. aquatic birds are the primary source of influenza a virus (iav), which is also widespread in various mammals, including humans and pigs. influenza b virus (ibv) and influenza c virus (icv) primarily infect humans, and influenza d virus (idv) is found in cattle and pigs. iav and ibv circulate in humans and cause seasonal epidemics, and icv causes a mild infection, primarily in children. idv can infect humans but is not known to cause illness. in humans, influenza viruses are primarily transmitted through respiratory droplets produced from coughing and sneezing. transmission through aerosols and intermediate objects and surfaces contaminated by the virus also occur. frequent hand washing and covering one's mouth and nose when coughing and sneezing reduce transmission. annual vaccination can help to provide protection against influenza. influenza viruses, particularly iav, evolve quickly, so flu vaccines are updated regularly to match which influenza strains are in circulation. vaccines provide protection against iav subtypes h1n1 and h3n2 and one or two ibv subtypes. influenza infection is diagnosed with laboratory methods such as antibody or antigen tests and a polymerase chain reaction (pcr) to identify viral nucleic acid. the disease can be treated with supportive measures and, in severe cases, with antiviral drugs such as oseltamivir. in healthy individuals, influenza is typically self-limiting and rarely fatal, but it can be deadly in high-risk groups. in a typical year, 5–15% of the population contracts influenza. there are 3–5 million severe cases annually, with up to 650,000 respiratory-related deaths globally each year. deaths most commonly occur in high-risk groups, including young children, the elderly, and people with chronic health conditions. in temperate regions of the world, the number of influenza cases peaks during winter, whereas in the tropics influenza can occur year-round. since the late 1800s, large outbreaks of novel influenza strains that spread globally, called pandemics, have occurred every 10–50 years. five flu pandemics have occurred since 1900: the spanish flu in 1918–1920, which was the most severe flu pandemic, the asian flu in 1957, the hong kong flu in 1968, the russian flu in 1977, and the swine flu pandemic in 2009. signs and symptoms symptoms of influenza, with fever and cough the most common symptoms the time between exposure to the virus and development of symptoms, called the incubation period, is 1–4 days, most commonly 1–2 days. many infections, however, are asymptomatic. the onset of symptoms is sudden, and initial symptoms are predominately non-specific, including fever, chills, headaches, muscle pain or aching, a feeling of discomfort, loss of appetite, lack of energy/fatigue, and confusion. these symptoms are usually accompanied by respiratory symptoms such as a dry cough, sore or dry throat, hoarse voice, and a stuffy or runny nose. coughing is the most common symptom. gastrointestinal symptoms may also occur, including nausea, vomiting, diarrhea, and gastroenteritis, especially in children. the standard influenza symptoms typically last for 2–8 days. a 2021 study suggests influenza can cause long lasting symptoms in a similar way to long covid. symptomatic infections are usually mild and limited to the upper respiratory tract, but progression to pneumonia is relatively common. pneumonia may be caused by the primary viral infection or by a secondary bacterial infection. primary pneumonia is characterized by rapid progression of fever, cough, labored breathing, and low oxygen levels that cause bluish skin. it is especially common among those who have an underlying cardiovascular disease such as rheumatic heart disease. secondary pneumonia typically has a period of improvement in symptoms for 1–3 weeks followed by recurrent fever, sputum production, and fluid buildup in the lungs, but can also occur just a few days after influenza symptoms appear. about a third of primary pneumonia cases are followed by secondary pneumonia, which is most frequently caused by the bacteria streptococcus pneumoniae and staphylococcus aureus. virology types of virus influenza virus nomenclature (for a fujian flu virus) influenza viruses comprise four species. each of the four species is the sole member of its own genus, and the four influenza genera comprise four of the seven genera in the family orthomyxoviridae. they are: influenza a virus (iav), genus alphainfluenzavirus influenza b virus (ibv), genus betainfluenzavirus influenza c virus (icv), genus gammainfluenzavirus influenza d virus (idv), genus deltainfluenzavirus iav is responsible for most cases of severe illness as well as seasonal epidemics and occasional pandemics. it infects people of all ages but tends to disproportionately cause severe illness in the elderly, the very young, and those who have chronic health issues. birds are the primary reservoir of iav, especially aquatic birds such as ducks, geese, shorebirds, and gulls, but the virus also circulates among mammals, including pigs, horses, and marine mammals. iav is classified into subtypes based on the viral proteins haemagglutinin (h) and neuraminidase (n). as of 2019, 18 h subtypes and 11 n subtypes have been identified. most potential combinations have been reported in birds, but h17-18 and n10-11 have only been found in bats. only h subtypes h1-3 and n subtypes n1-2 are known to have circulated in humans. the iav subtypes in circulation as of 2018 are h1n1 and h3n2. iavs can be classified more specifically by natural host species, geographical origin, year of isolation, and strain number, such as h1n1/a/duck/alberta/35/76. ibv mainly infects humans but has been identified in seals, horses, dogs, and pigs. ibv does not have subtypes like iav but has two antigenically distinct lineages, termed the b/victoria/2/1987-like and b/yamagata/16/1988-like lineages, or simply (b/)victoria(-like) and (b/)yamagata(-like). both lineages are in circulation in humans, disproportionately affecting children. ibvs contribute to seasonal epidemics alongside iavs but have never been associated with a pandemic. icv, like ibv, is primarily found in humans, though it also has been detected in pigs, feral dogs, dromedary camels, cattle, and dogs. icv infection primarily affects children and is usually asymptomatic or has mild cold-like symptoms, though more severe symptoms such as gastroenteritis and pneumonia can occur. unlike iav and ibv, icv has not been a major focus of research pertaining to antiviral drugs, vaccines, and other measures against influenza. icv is subclassified into six genetic/antigenic lineages. idv has been isolated from pigs and cattle, the latter being the natural reservoir. infection has also been observed in humans, horses, dromedary camels, and small ruminants such as goats and sheep. idv is distantly related to icv. while cattle workers have occasionally tested positive to prior idv infection, it is not known to cause disease in humans. icv and idv experience a slower rate of antigenic evolution than iav and ibv. because of this antigenic stability, relatively few novel lineages emerge. genome and structure structure of the influenza virion. the hemagglutinin (ha) and neuraminidase (na) proteins are shown on the surface of the particle. the viral rnas that make up the genome are shown as red coils inside the particle and bound to ribonucleoproteins (rnp). influenza viruses have a negative-sense, single-stranded rna genome that is segmented. the negative sense of the genome means it can be used as a template to synthesize messenger rna (mrna). iav and ibv have eight genome segments that encode 10 major proteins. icv and idv have seven genome segments that encode nine major proteins. three segments encode three subunits of an rna-dependent rna polymerase (rdrp) complex: pb1, a transcriptase, pb2, which recognizes 5' caps, and pa (p3 for icv and idv), an endonuclease. the matrix protein (m1) and membrane protein (m2) share a segment, as do the non-structural protein (ns1) and the nuclear export protein (nep). for iav and ibv, hemagglutinin (ha) and neuraminidase (na) are encoded on one segment each, whereas icv and idv encode a hemagglutinin-esterase fusion (hef) protein on one segment that merges the functions of ha and na. the final genome segment encodes the viral nucleoprotein (np). influenza viruses also encode various accessory proteins, such as pb1-f2 and pa-x, that are expressed through alternative open reading frames and which are important in host defense suppression, virulence, and pathogenicity. the virus particle, called a virion, is pleomorphic and varies between being filamentous, bacilliform, or spherical in shape. clinical isolates tend to be pleomorphic, whereas strains adapted to laboratory growth typically produce spherical virions. filamentous virions are about 250 nanometers (nm) by 80 nm, bacilliform 120–250 by 95 nm, and spherical 120 nm in diameter. the virion consists of each segment of the genome bound to nucleoproteins in separate ribonucleoprotein (rnp) complexes for each segment, all of which are surrounded by a lipid bilayer membrane called the viral envelope. there is a copy of the rdrp, all subunits included, bound to each rnp. the envelope is reinforced structurally by matrix proteins on the interior that enclose the rnps, and the envelope contains ha and na (or hef) proteins extending outward from the exterior surface of the envelope. ha and hef proteins have a distinct "head" and "stalk" structure. m2 proteins form proton ion channels through the viral envelope that are required for viral entry and exit. ibvs contain a surface protein named nb that is anchored in the envelope, but its function is unknown. life cycle host cell invasion and replication by the influenza virus the viral life cycle begins by binding to a target cell. binding is mediated by the viral ha proteins on the surface of the envelope, which bind to cells that contain sialic acid receptors on the surface of the cell membrane. for n1 subtypes with the "g147r" mutation and n2 subtypes, the na protein can initiate entry. prior to binding, na proteins promote access to target cells by degrading mucus, which helps to remove extracellular decoy receptors that would impede access to target cells. after binding, the virus is internalized into the cell by an endosome that contains the virion inside it. the endosome is acidified by cellular vatpase to have lower ph, which triggers a conformational change in ha that allows fusion of the viral envelope with the endosomal membrane. at the same time, hydrogen ions diffuse into the virion through m2 ion channels, disrupting internal protein-protein interactions to release rnps into the host cell's cytosol. the m1 protein shell surrounding rnps is degraded, fully uncoating rnps in the cytosol. rnps are then imported into the nucleus with the help of viral localization signals. there, the viral rna polymerase transcribes mrna using the genomic negative-sense strand as a template. the polymerase snatches 5' caps for viral mrna from cellular rna to prime mrna synthesis and the 3'-end of mrna is polyadenylated at the end of transcription. once viral mrna is transcribed, it is exported out of the nucleus and translated by host ribosomes in a cap-dependent manner to synthesize viral proteins. rdrp also synthesizes complementary positive-sense strands of the viral genome in a complementary rnp complex which are then used as templates by viral polymerases to synthesize copies of the negative-sense genome. during these processes, rdrps of avian influenza viruses (aivs) function optimally at a higher temperature than mammalian influenza viruses. newly synthesized viral polymerase subunits and np proteins are imported to the nucleus to further increase the rate of viral replication and form rnps. ha, na, and m2 proteins are trafficked with the aid of m1 and nep proteins to the cell membrane through the golgi apparatus and inserted into the cell's membrane.