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 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.
There are four types of influenza virus: types A, B, C, and D. Aquatic birds are the primary source of influenza A virus, which is also widespread in various mammals, including humans and pigs. Influenza B virus and influenza C virus primarily infect humans, and influenza D virus is found in cattle and pigs. Influenza A virus and influenza B virus circulate in humans and cause seasonal epidemics, and influenza C virus causes a mild infection, primarily in children. Influenza D virus can infect humans but is not known to cause illness. In humans, influenza viruses are primarily transmitted through respiratory droplets from coughing and sneezing. Transmission through aerosols and surfaces contaminated by the virus also occur.
Frequent hand washing and covering one's mouth and nose when coughing and sneezing reduce transmission, as does wearing a mask. Annual vaccination can help to provide protection against influenza. Influenza viruses, particularly influenza A virus, evolve quickly, so flu vaccines are updated regularly to match which influenza strains are in circulation. Vaccines provide protection against influenza A virus subtypes H1N1 and H3N2 and one or two influenza B virus subtypes. Influenza infection is diagnosed with laboratory methods such as antibody or antigen tests and a polymerase chain reaction 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, five to 15 percent of the population contracts influenza. There are 3 to 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, the number of influenza cases peaks during winter, whereas in the tropics, influenza can occur year-round. Since the late 1800s, pandemic outbreaks of novel influenza strains have occurred every 10 to 50 years. Five flu pandemics have occurred since 1900: the Spanish flu from 1918 to 1920, which was the most severe; 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
The symptoms of influenza are similar to those of a cold, although usually more severe and less likely to include a runny nose. The time between exposure to the virus and development of symptoms is one to four days, most commonly one to two days. Many infections are asymptomatic. The onset of symptoms is sudden, and initial symptoms are predominantly non-specific, including fever, chills, headaches, muscle pain, malaise, loss of appetite, lack of energy, and confusion. These 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 two to eight days. Some studies suggest 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 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 one to three 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 viruses comprise four species, each the sole member of its own genus. The four influenza genera comprise four of the seven genera in the family Orthomyxoviridae. They are:- Influenza A virus, genus Alphainfluenzavirus
- Influenza B virus, genus Betainfluenzavirus
- Influenza C virus, genus Gammainfluenzavirus
- Influenza D virus, genus Deltainfluenzavirus
Subtypes of Influenza A are defined by the combination of the antigenic viral proteins haemagglutinin and neuraminidase in the viral envelope; for example, "H1N1" designates an IAV subtype that has a type-1 hemagglutinin protein and a type-1 neuraminidase protein. Almost all possible combinations of H and N have been isolated from wild birds. In addition H17, H18, N10 and N11 have been found in bats. The influenza A virus subtypes in circulation among humans are H1N1 and H3N2.
Influenza B virus mainly infects humans but has been identified in seals, horses, dogs, and pigs. Influenza B virus does not have subtypes like influenza A virus but has two antigenically distinct lineages, termed the B/Victoria/2/1987-like and B/Yamagata/16/1988-like lineages, or simply Victoria and Yamagata. Both lineages are in circulation in humans, disproportionately affecting children. However, the B/Yamagata lineage might have become extinct in 2020/2021 due to COVID-19 pandemic measures. Influenza B viruses contribute to seasonal epidemics alongside influenza A viruses but have never been associated with a pandemic.
Influenza C virus, like influenza B virus, is primarily found in humans, though it has been detected in pigs, feral dogs, dromedary camels, cattle, and dogs. Influenza C virus 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 influenza A virus and influenza B virus, influenza C virus has not been a major focus of research pertaining to antiviral drugs, vaccines, and other measures against influenza. Influenza C virus is subclassified into six genetic/antigenic lineages.
Influenza D virus 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. Influenza D virus is distantly related to influenza C virus. While cattle workers have occasionally tested positive to prior influenza D virus infection, it is not known to cause disease in humans. Influenza C virus and influenza D virus experience a slower rate of antigenic evolution than influenza A virus and influenza B virus. Because of this antigenic stability, relatively few novel lineages emerge.
Influenza virus nomenclature
Every year, millions of influenza virus samples are analysed to monitor changes in the virus' antigenic properties, and to inform the development of vaccines.To unambiguously describe a specific isolate of virus, researchers use the internationally accepted influenza virus nomenclature, which describes, among other things, the species of animal from which the virus was isolated, and the place and year of collection. As an example – "A/chicken/Nakorn-Patom/Thailand/CU-K2/04":
- "A" stands for the genus of influenza.
- "chicken" is the animal species the isolate was found in
- "Nakorn-Patom/Thailand" is the place this specific virus was isolated
- "CU-K2" is the laboratory reference number that identifies it from other influenza viruses isolated at the same place and year
- "04" represents the year of isolation 2004
- "H5" stands for the fifth of several known types of the protein hemagglutinin.
- "N1" stands for the first of several known types of the protein neuraminidase.
Genome and structure
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. Influenza A virus and influenza B virus have eight genome segments that encode 10 major proteins. Influenza C virus and influenza D virus have seven genome segments that encode nine major proteins.Three segments encode three subunits of an RNA-dependent RNA polymerase complex: PB1, a transcriptase, PB2, which recognizes 5' caps, and PA, an endonuclease. The M1 matrix protein and M2 proton channel share a segment, as do the non-structural protein and the nuclear export protein. For influenza A virus and influenza B virus, hemagglutinin and neuraminidase are encoded on one segment each, whereas influenza C virus and influenza D virus encode a hemagglutinin-esterase fusion protein on one segment that merges the functions of HA and NA. The final genome segment encodes the viral nucleoprotein. 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 by 80 nm, bacilliform 120–250 by 95 nm, and spherical 120 nm in diameter.
The core of the virion comprises one copy of each segment of the genome bound to NP nucleoproteins in separate ribonucleoprotein complexes for each segment. There is a copy of the RdRp, all subunits included, bound to each RNP. The genetic material is encapsulated by a layer of M1 matrix protein which provides structural reinforcement to the outer layer, the viral envelope. The envelope comprises a lipid bilayer membrane incorporating HA and NA proteins extending outward from its exterior surface. HA and HEF proteins have a distinct "head" and "stalk" structure. M2 proteins form proton channels through the viral envelope that are required for viral entry and exit. Influenza B viruses contain a surface protein named NB that is anchored in the envelope, but its function is unknown.