Orthomyxoviridae
Encyclopedia
The Orthomyxoviridae are a family of RNA virus
es that includes five genera
: Influenzavirus A, Influenzavirus B
, Influenzavirus C
, Isavirus and Thogotovirus
. A sixth has recently been described. The first three genera contain viruses that cause influenza
in vertebrates, including bird
s (see also avian influenza), humans, and other mammal
s. Isaviruses infect salmon; thogotoviruses infect vertebrate
s and invertebrate
s, such as mosquito
es and sea lice
.
The three genera of Influenzavirus, which are identified by antigenic differences in their nucleoprotein
and matrix protein
infect vertebrates as follows:
the "RNA virus
es" includes the "negative-sense ssRNA viruses
" which includes the Order "Mononegavirales
", and the Family "Orthomyxoviridae" (among others). The genera-associated species and serotypes of Orthomyxoviridae are shown in the following table.
, Influenzavirus C
and Ryanovirus. Each genus includes only one species, or type: Influenza A virus, Influenza B virus, and Influenza C virus, respectively. Influenza A and C infect multiple species, while influenza B almost exclusively infects humans.
(HA or H) and neuraminidase
(NA or N)... Sixteen H subtypes (or serotypes) and nine N subtypes of influenza A virus have been identified.
Further variation exists; thus, specific influenza strain isolates are identified by a standard nomenclature specifying virus type, geographical location where first isolated, sequential number of isolation, year of isolation, and HA and NA subtype.
Examples of the nomenclature are:
The type A viruses are the most virulent human pathogens among the three influenza types and causes the most severe disease. The serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:
. This type of influenza mutates at a rate 2-3 times lower than type A and consequently is less genetically diverse, with only one influenza B serotype. As a result of this lack of antigen
ic diversity, a degree of immunity to influenza B is usually acquired at an early age. However, influenza B mutates enough that lasting immunity is not possible. This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift
), ensures that pandemics of influenza B do not occur.
s and pig
s, and can cause severe illness and local epidemic
s. However, influenza C is less common than the other types and usually seems to cause mild disease in children.
The virion is pleomorphic, the envelope can occur in spherical and filamentous forms. In general the virus's morphology is spherical with particles 50 to 120 nm in diameter, or filamentous virions 20 nm in diameter and 200 to 300 (-3000) nm long. There are some 500 distinct spike-like surface projections of the envelope each projecting 10 to 14 nm from the surface with some types (i.e. hemagglutinin esterase (HEF)) densely dispersed over the surface, and with others (i.e. hemagglutinin
(HA)) spaced widely apart.
The major glycoprotein
(HA) is interposed irregularly by clusters of neuraminidase
(NA), with a ratio of HA to NA of about 4-5 to 1.
Lipoprotein
membranes enclose the nucleocapsid
s; nucleoproteins of different size classes with a loop at each end; the arrangement within the virion is uncertain. The nucleocapsids are filamentous and fall in the range of 50 to 130 nm long and 9 to 15 nm in diameter. They have a helical symmetry.
single stranded RNA.
The total genome length is 12000-15000 nucleotide
s (nt). The largest segment 2300-2500 nt; of second largest 2300-2500 nt; of third 2200-2300 nt; of fourth 1700-1800 nt; of fifth 1500-1600 nt; of sixth 1400-1500 nt; of seventh 1000-1100 nt; of eighth 800-900 nt. Genome sequence has terminal repeated sequences; repeated at both ends. Terminal repeats at the 5'-end 12-13 nucleotides long. Nucleotide sequences of 3'-terminus identical; the same in genera of same family; most on RNA (segments), or on all RNA species. Terminal repeats at the 3'-end 9-11 nucleotides long. Encapsidated nucleic acid is solely genomic. Each virion may contain defective interfering copies.
The influenza A virus particle or virion is 80-120 nm in diameter and usually roughly spherical, although filamentous forms can occur. Unusually for a virus, the influenza A genome
is not a single piece of nucleic acid; instead, it contains eight pieces of segmented negative-sense RNA
(13.5 kilobases total), which encode 11 proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2). The best-characterised of these viral proteins are hemagglutinin
and neuraminidase
, two large glycoprotein
s found on the outside of the viral particles. Neuraminidase is an enzyme
involved in the release of progeny
virus from infected cells, by cleaving sugars that bind the mature viral particles. By contrast, hemagglutinin is a lectin
that mediates binding of the virus to target cells and entry of the viral genome into the target cell. The hemagglutinin (H) and neuraminidase (N) protein
s are targets for antiviral drugs. These proteins are also recognised by antibodies
, i.e. they are antigen
s. The responses of antibodies to these proteins are used to classify the different serotype
s of influenza A viruses, hence the H and N in H5N1.
Typically, influenza is transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus, and from infected birds through their droppings
. Influenza can also be transmitted by saliva
, nasal secretions
, feces
and blood
. Infections occur through contact with these bodily fluids or with contaminated surfaces. Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0 °C (32 °F), and indefinitely at very low temperatures (such as lakes in northeast Siberia
). They can be inactivated easily by disinfectants and detergent
s.
The viruses bind to a cell through interactions between its hemagglutinin
glycoprotein and sialic acid
sugars on the surfaces of epithelial cells
in the lung and throat (Stage 1 in infection figure). The cell imports the virus by endocytosis
. In the acidic endosome
, part of the haemagglutinin protein fuses the viral envelope with the vacuole's membrane, releasing the viral RNA (vRNA) molecules, accessory proteins and RNA-dependent RNA polymerase into the cytoplasm
(Stage 2). These proteins and vRNA form a complex that is transported into the cell nucleus
, where the RNA-dependent RNA transcriptase begins transcribing complementary positive-sense cRNA (Steps 3a and b). The cRNA is either exported into the cytoplasm and translated (step 4), or remains in the nucleus. Newly-synthesised viral proteins are either secreted through the Golgi apparatus
onto the cell surface (in the case of neuraminidase and hemagglutinin, step 5b) or transported back into the nucleus to bind vRNA and form new viral genome particles (step 5a). Other viral proteins have multiple actions in the host cell, including degrading cellular mRNA and using the released nucleotide
s for vRNA synthesis and also inhibiting translation of host-cell mRNAs.
Negative-sense vRNAs that form the genome
s of future viruses, RNA-dependent RNA transcriptase, and other viral proteins are assembled into a virion. Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. The vRNA and viral core proteins leave the nucleus and enter this membrane protrusion (step 6). The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7). As before, the viruses adhere to the cell through hemagglutinin; the mature viruses detach once their neuraminidase
has cleaved sialic acid residues from the host cell. After the release of new influenza virus, the host cell dies.
Since RNA proofreading enzymes are absent, the RNA-dependent RNA transcriptase makes a single nucleotide insertion error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA. Hence, nearly every newly-manufactured influenza virus will contain a mutation in its genome. The separation of the genome into eight separate segments of vRNA allows mixing (reassortment
) of the genes if more than one variety of influenza virus has infected the same cell (superinfection
). The resulting alteration in the genome segments packaged in to viral progeny confers new behavior, sometimes the ability to infect new host species or to overcome protective immunity of host populations to its old genome (in which case it is called an antigenic shift
).
However, when the antigenicities of the seed strains and wild viruses do not match, vaccines fail to protect the vaccinees. In addition, even when they do match, escape mutants are often generated. The drugs include amantadine, which inhibits the uncoating of virions by interfering with M2, and oseltamivir (marketed under the brand name Tamiflu), which inhibits the release of virions from infected cells by interfering with NA. However, escape mutants are often generated for the former drug and less frequently for the latter drug.
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...
es that includes five genera
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
: Influenzavirus A, Influenzavirus B
Influenzavirus B
Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".Influenza B viruses are only known to infect humans and seals, giving them influenza...
, Influenzavirus C
Influenzavirus C
Influenzavirus C is a genus in the virus family Orthomyxoviridae, which includes those viruses which cause influenza. The only species in this genus is called "Influenza C virus".Influenza C viruses are known to infect humans and pigs, giving them influenza...
, Isavirus and Thogotovirus
Thogotovirus
Thogotovirus is a genus in the virus family Orthomyxoviridae. It can replicate in both tick cells and vertebrate cells and is usually transmitted by ticks....
. A sixth has recently been described. The first three genera contain viruses that cause influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
in vertebrates, including bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s (see also avian influenza), humans, and other mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s. Isaviruses infect salmon; thogotoviruses infect vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s and invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
s, such as mosquito
Mosquito
Mosquitoes are members of a family of nematocerid flies: the Culicidae . The word Mosquito is from the Spanish and Portuguese for little fly...
es and sea lice
Sea lice
The sea louse is a copepod within the order Siphonostomatoida, family Caligidae. There are 36 genera within this family which include approximately 42 Lepeophtheirus and 300 Caligus species...
.
The three genera of Influenzavirus, which are identified by antigenic differences in their nucleoprotein
Nucleoprotein
A nucleoprotein is any protein that is structurally associated with nucleic acid .Many viruses harness this protein, and they are known for being host-specific...
and matrix protein
Matrix protein
Viral matrix proteins are non structural proteins linking the viral envelope with the virus core. They play a crucial role in virus assembly, and interact with the RNP complex as well as with the viral membrane...
infect vertebrates as follows:
- Influenzavirus AInfluenzavirus AInfluenza A virus causes influenza in birds and some mammals and is the only species of Influenzavirus A. Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon...
infects humans, other mammals, and birds, and causes all flu pandemics - Influenzavirus BInfluenzavirus BInfluenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".Influenza B viruses are only known to infect humans and seals, giving them influenza...
infects humans and sealPinnipedPinnipeds or fin-footed mammals are a widely distributed and diverse group of semiaquatic marine mammals comprising the families Odobenidae , Otariidae , and Phocidae .-Overview: Pinnipeds are typically sleek-bodied and barrel-shaped...
s - Influenzavirus CInfluenzavirus CInfluenzavirus C is a genus in the virus family Orthomyxoviridae, which includes those viruses which cause influenza. The only species in this genus is called "Influenza C virus".Influenza C viruses are known to infect humans and pigs, giving them influenza...
infects humans and pigPigA pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
s
Classification
In a phylogenetic-based taxonomyTaxonomy
Taxonomy is the science of identifying and naming species, and arranging them into a classification. The field of taxonomy, sometimes referred to as "biological taxonomy", revolves around the description and use of taxonomic units, known as taxa...
the "RNA virus
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...
es" includes the "negative-sense ssRNA viruses
Sense (molecular biology)
In molecular biology and genetics, sense is a concept used to compare the polarity of nucleic acid molecules, such as DNA or RNA, to other nucleic acid molecules...
" which includes the Order "Mononegavirales
Mononegavirales
The order Mononegavirales is the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. All of these viruses cause significant disease in...
", and the Family "Orthomyxoviridae" (among others). The genera-associated species and serotypes of Orthomyxoviridae are shown in the following table.
| Genus Genus In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia... |
Species Species In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are... (* indicates type species Type species In biological nomenclature, a type species is both a concept and a practical system which is used in the classification and nomenclature of animals and plants. The value of a "type species" lies in the fact that it makes clear what is meant by a particular genus name. A type species is the species... ) |
Serotypes or Subtypes | Hosts Host (biology) In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna... |
|---|---|---|---|
| Influenzavirus A | Influenza A virus* | H1N1 H1N1 'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of... , H1N2 H1N2 H1N2 is a subtype of the species Influenza A virus . It is currently pandemic in both human and pig populations.H1N1, H1N2, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans.... , H2N2 H2N2 H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds... , H3N1, H3N2 H3N2 Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains... , H3N8 H3N8 H3N8 is a subtype of the species Influenza A virus that is endemic in birds, horses and dogs.-Introduction:Equine influenza is a highly contagious respiratorydisease of horses and related animals such as donkeys,... , H5N1 H5N1 Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species... , H5N2 H5N2 H5N2 is a subtype of the species Influenzavirus A .-H5N2 and birds:Low pathogenic avian inluenza H5N2 virus in poultry later gained accentuated virulence in the United States and Mexico... , H5N3 H5N3 H5N3 is a subtype of the species Influenza A virus .H5N3 was identified in Quebec in August 2005 and in Sweden in October 2005.2009:... , H5N8 H5N8 H5N8 is a subtype of the species Influenza A virus .A highly pathogenic strain of it called A/turkey/Ireland/1378/83 caused a minor flu outbreak in 1983 in Ireland in turkeys.... , H5N9 H5N9 H5N9 is a subtype of the species Influenza A virus .A highly pathogenic strain of H5N9 caused a minor flu outbreak in 1966 in Ontario and Manitoba, Canada in turkeys.... , H7N1 H7N1 H7N1 is a subtype of the species Influenza A virus .A highly pathogenic strain of it caused a flu outbreak with significant spread to numerous farms, resulting in great economic losses in 1999 in Italy in turkeys.... , H7N2 H7N2 H7N2 is a subtype of the species Influenza A virus .A CDC study following outbreaks of H7N2 in commercial poultry farms in western Virginia in 2002 concluded:... , H7N3 H7N3 H7N3 is a subtype of the species Influenza A virus .In North America, the presence of H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans infected with it have been... , H7N4 H7N4 H7N4 is a subtype of the species Influenza A virus .A highly pathogenic strain of it caused a minor flu outbreak in 1997 in New South Wales, Australia in chicken.... , H7N7 H7N7 H7N7 is a subtype of Influenzavirus A, a genus of Orthomyxovirus, the viruses responsible for influenza. Highly pathogenic strains and low pathogenic strains exist. H7N7 can infect humans, birds, pigs, seals, and horses in the wild; and has infected mice in laboratory studies... , H9N2 H9N2 H9N2 is a subtype of the species Influenza A virus ."H9N2 influenza viruses of domestic ducks have become established in the domestic poultry of Asia. Phylogenetic and antigenic analyses of the H9N2 viruses isolated from Hong Kong markets suggest three distinct sublineages... , H10N7 H10N7 H10N7 is a subtype of the species Influenza A virus . In 2004 in Egypt, H10N7 was reported for the first time in humans. It caused illness in two one-year old infants, residents of Ismaillia, Egypt; one child’s father a poultry merchant.The first reported H10N7 outbreak in the US occurred in... |
Human Human Humans are the only living species in the Homo genus... , pig Pig A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives... , bird Bird Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from... , horse Horse The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today... |
| Influenzavirus B Influenzavirus B Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".Influenza B viruses are only known to infect humans and seals, giving them influenza... |
Influenza B virus* | Human, seal Earless seal The true seals or earless seals are one of the three main groups of mammals within the seal superfamily, Pinnipedia. All true seals are members of the family Phocidae . They are sometimes called crawling seals to distinguish them from the fur seals and sea lions of the family Otariidae... |
|
| Influenzavirus C Influenzavirus C Influenzavirus C is a genus in the virus family Orthomyxoviridae, which includes those viruses which cause influenza. The only species in this genus is called "Influenza C virus".Influenza C viruses are known to infect humans and pigs, giving them influenza... |
Influenza C virus* | Human, pig | |
| Isavirus | Infectious salmon anemia Infectious salmon anemia Infectious salmon anemia or anaemia is a viral disease of Atlantic Salmon that affects fish farms in Canada, Norway, Scotland and Chile, causing severe losses to infected farms... virus* |
Atlantic salmon Atlantic salmon The Atlantic salmon is a species of fish in the family Salmonidae, which is found in the northern Atlantic Ocean and in rivers that flow into the north Atlantic and the north Pacific.... |
|
| Thogotovirus Thogotovirus Thogotovirus is a genus in the virus family Orthomyxoviridae. It can replicate in both tick cells and vertebrate cells and is usually transmitted by ticks.... |
Thogoto virus* | Tick Tick Ticks are small arachnids in the order Ixodida, along with mites, constitute the subclass Acarina. Ticks are ectoparasites , living by hematophagy on the blood of mammals, birds, and sometimes reptiles and amphibians... , mosquito Mosquito Mosquitoes are members of a family of nematocerid flies: the Culicidae . The word Mosquito is from the Spanish and Portuguese for little fly... , mammal Mammal Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young... (including human) |
|
| Dhori virus Dhori virus Dhori virus is a species of the genus Thogotovirus. Its hosts are ticks, mosquitos, and mammals .... |
Batken virus, Dhori virus Dhori virus Dhori virus is a species of the genus Thogotovirus. Its hosts are ticks, mosquitos, and mammals .... |
||
| Quaranfil virus, Johnston Atoll virus, Lake Chad virus | |||
Types
There are four genera of influenza virus: Influenzavirus A, Influenzavirus BInfluenzavirus B
Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".Influenza B viruses are only known to infect humans and seals, giving them influenza...
, Influenzavirus C
Influenzavirus C
Influenzavirus C is a genus in the virus family Orthomyxoviridae, which includes those viruses which cause influenza. The only species in this genus is called "Influenza C virus".Influenza C viruses are known to infect humans and pigs, giving them influenza...
and Ryanovirus. Each genus includes only one species, or type: Influenza A virus, Influenza B virus, and Influenza C virus, respectively. Influenza A and C infect multiple species, while influenza B almost exclusively infects humans.
Influenza A
Influenza A viruses are further classified, based on the viral surface proteins hemagglutininHemagglutinin
Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
(HA or H) and neuraminidase
Neuraminidase
Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...
(NA or N)... Sixteen H subtypes (or serotypes) and nine N subtypes of influenza A virus have been identified.
Examples of the nomenclature are:
- A/Brisbane/59/2007 (H1N1)
- A/Moscow/10/99 (H3N2)
The type A viruses are the most virulent human pathogens among the three influenza types and causes the most severe disease. The serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:
- H1N1H1N1'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...
caused "Spanish FluSpanish fluThe 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...
" in 1918, "Swine fluSwine fluSwine influenza, also called pig influenza, swine flu, hog flu and pig flu, is an infection by any one of several types of swine influenza virus. Swine influenza virus or S-OIV is any strain of the influenza family of viruses that is endemic in pigs...
" in 2009. - H2N2H2N2H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds...
caused "Asian Flu". - H3N2H3N2Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...
caused "Hong Kong Flu". - H5N1H5N1Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
is a pandemicPandemicA pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...
threat. - H7N7H7N7H7N7 is a subtype of Influenzavirus A, a genus of Orthomyxovirus, the viruses responsible for influenza. Highly pathogenic strains and low pathogenic strains exist. H7N7 can infect humans, birds, pigs, seals, and horses in the wild; and has infected mice in laboratory studies...
has unusual zoonotic potential. - H1N2H1N2H1N2 is a subtype of the species Influenza A virus . It is currently pandemic in both human and pig populations.H1N1, H1N2, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans....
is endemic in humans and pigs. - H9N2H9N2H9N2 is a subtype of the species Influenza A virus ."H9N2 influenza viruses of domestic ducks have become established in the domestic poultry of Asia. Phylogenetic and antigenic analyses of the H9N2 viruses isolated from Hong Kong markets suggest three distinct sublineages...
, H7N2H7N2H7N2 is a subtype of the species Influenza A virus .A CDC study following outbreaks of H7N2 in commercial poultry farms in western Virginia in 2002 concluded:...
, H7N3H7N3H7N3 is a subtype of the species Influenza A virus .In North America, the presence of H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans infected with it have been...
, H10N7H10N7H10N7 is a subtype of the species Influenza A virus . In 2004 in Egypt, H10N7 was reported for the first time in humans. It caused illness in two one-year old infants, residents of Ismaillia, Egypt; one child’s father a poultry merchant.The first reported H10N7 outbreak in the US occurred in...
.
| Name | Year | Deaths (millions) | Subtype involved |
|---|---|---|---|
| Asiatic (Russian) Flu | 1889-90 | 1 | possibly H2N2 H2N2 H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds... |
| Spanish Flu Spanish flu The 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin... |
1918-20 | 40 | H1N1 H1N1 'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of... |
| Asian Flu Asian flu Asian Flu may refer to:* The Asian Financial Crisis of 1997, or* Asian Flu, the H2N2 virus... |
1957-58 | 1-1.5 | H2N2 H2N2 H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds... |
| Hong Kong Flu Hong Kong flu The Hong Kong flu was a category 2 flu pandemic whose outbreak in 1968 and 1969 killed an estimated one million people worldwide. It was caused by an H3N2 strain of the influenza A virus, descended from H2N2 through antigenic shift, a genetic process in which genes from multiple subtypes reassorted... |
1968-69 | 0.75 | H3N2 H3N2 Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains... |
| Swine Flu | 2009 - | ... | H1N1 H1N1 'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of... |
Influenza B
Influenza B virus is almost exclusively a human pathogen, and is less common than influenza A. The only other animal known to be susceptible to influenza B infection is the sealPinniped
Pinnipeds or fin-footed mammals are a widely distributed and diverse group of semiaquatic marine mammals comprising the families Odobenidae , Otariidae , and Phocidae .-Overview: Pinnipeds are typically sleek-bodied and barrel-shaped...
. This type of influenza mutates at a rate 2-3 times lower than type A and consequently is less genetically diverse, with only one influenza B serotype. As a result of this lack of antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
ic diversity, a degree of immunity to influenza B is usually acquired at an early age. However, influenza B mutates enough that lasting immunity is not possible. This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift
Antigenic shift
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...
), ensures that pandemics of influenza B do not occur.
Influenza C
The influenza C virus infects humanHuman
Humans are the only living species in the Homo genus...
s and pig
Pig
A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
s, and can cause severe illness and local epidemic
Epidemic
In epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...
s. However, influenza C is less common than the other types and usually seems to cause mild disease in children.
Morphology
Hemagglutinin
Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
(HA)) spaced widely apart.
The major glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
(HA) is interposed irregularly by clusters of neuraminidase
Neuraminidase
Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...
(NA), with a ratio of HA to NA of about 4-5 to 1.
Lipoprotein
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
membranes enclose the nucleocapsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
s; nucleoproteins of different size classes with a loop at each end; the arrangement within the virion is uncertain. The nucleocapsids are filamentous and fall in the range of 50 to 130 nm long and 9 to 15 nm in diameter. They have a helical symmetry.
Genome
Viruses of this family contain 6 to 8 segments of linear negative-senseSense (molecular biology)
In molecular biology and genetics, sense is a concept used to compare the polarity of nucleic acid molecules, such as DNA or RNA, to other nucleic acid molecules...
single stranded RNA.
The total genome length is 12000-15000 nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
s (nt). The largest segment 2300-2500 nt; of second largest 2300-2500 nt; of third 2200-2300 nt; of fourth 1700-1800 nt; of fifth 1500-1600 nt; of sixth 1400-1500 nt; of seventh 1000-1100 nt; of eighth 800-900 nt. Genome sequence has terminal repeated sequences; repeated at both ends. Terminal repeats at the 5'-end 12-13 nucleotides long. Nucleotide sequences of 3'-terminus identical; the same in genera of same family; most on RNA (segments), or on all RNA species. Terminal repeats at the 3'-end 9-11 nucleotides long. Encapsidated nucleic acid is solely genomic. Each virion may contain defective interfering copies.
Structure
The following applies for Influenza A viruses, although other influenza strains are very similar in structure:The influenza A virus particle or virion is 80-120 nm in diameter and usually roughly spherical, although filamentous forms can occur. Unusually for a virus, the influenza A genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
is not a single piece of nucleic acid; instead, it contains eight pieces of segmented negative-sense RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
(13.5 kilobases total), which encode 11 proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2). The best-characterised of these viral proteins are hemagglutinin
Hemagglutinin
Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
and neuraminidase
Neuraminidase
Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...
, two large glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
s found on the outside of the viral particles. Neuraminidase is an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
involved in the release of progeny
Progeny
Progeny can refer to:*A genetic descendant or offspring*An academic progeny Other uses*Progeny Linux Systems*Progeny - an episode of the television series Stargate Atlantis...
virus from infected cells, by cleaving sugars that bind the mature viral particles. By contrast, hemagglutinin is a lectin
Lectin
Lectins are sugar-binding proteins that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection...
that mediates binding of the virus to target cells and entry of the viral genome into the target cell. The hemagglutinin (H) and neuraminidase (N) protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s are targets for antiviral drugs. These proteins are also recognised by antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
, i.e. they are antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s. The responses of antibodies to these proteins are used to classify the different serotype
Serotype
Serotype or serovar refers to distinct variations within a subspecies of bacteria or viruses. These microorganisms, viruses, or cells are classified together based on their cell surface antigens...
s of influenza A viruses, hence the H and N in H5N1.
Life cycle
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
. Influenza can also be transmitted by saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
, nasal secretions
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
, feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
and blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
. Infections occur through contact with these bodily fluids or with contaminated surfaces. Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0 °C (32 °F), and indefinitely at very low temperatures (such as lakes in northeast Siberia
Siberia
Siberia is an extensive region constituting almost all of Northern Asia. Comprising the central and eastern portion of the Russian Federation, it was part of the Soviet Union from its beginning, as its predecessor states, the Tsardom of Russia and the Russian Empire, conquered it during the 16th...
). They can be inactivated easily by disinfectants and detergent
Detergent
A detergent is a surfactant or a mixture of surfactants with "cleaning properties in dilute solutions." In common usage, "detergent" refers to alkylbenzenesulfonates, a family of compounds that are similar to soap but are less affected by hard water...
s.
The viruses bind to a cell through interactions between its hemagglutinin
Hemagglutinin
Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
glycoprotein and sialic acid
Sialic acid
Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid...
sugars on the surfaces of epithelial cells
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
in the lung and throat (Stage 1 in infection figure). The cell imports the virus by endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
. In the acidic endosome
Endosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
, part of the haemagglutinin protein fuses the viral envelope with the vacuole's membrane, releasing the viral RNA (vRNA) molecules, accessory proteins and RNA-dependent RNA polymerase into the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
(Stage 2). These proteins and vRNA form a complex that is transported into the cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, where the RNA-dependent RNA transcriptase begins transcribing complementary positive-sense cRNA (Steps 3a and b). The cRNA is either exported into the cytoplasm and translated (step 4), or remains in the nucleus. Newly-synthesised viral proteins are either secreted through the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
onto the cell surface (in the case of neuraminidase and hemagglutinin, step 5b) or transported back into the nucleus to bind vRNA and form new viral genome particles (step 5a). Other viral proteins have multiple actions in the host cell, including degrading cellular mRNA and using the released nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
s for vRNA synthesis and also inhibiting translation of host-cell mRNAs.
Negative-sense vRNAs that form the genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
s of future viruses, RNA-dependent RNA transcriptase, and other viral proteins are assembled into a virion. Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. The vRNA and viral core proteins leave the nucleus and enter this membrane protrusion (step 6). The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7). As before, the viruses adhere to the cell through hemagglutinin; the mature viruses detach once their neuraminidase
Neuraminidase
Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...
has cleaved sialic acid residues from the host cell. After the release of new influenza virus, the host cell dies.
Since RNA proofreading enzymes are absent, the RNA-dependent RNA transcriptase makes a single nucleotide insertion error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA. Hence, nearly every newly-manufactured influenza virus will contain a mutation in its genome. The separation of the genome into eight separate segments of vRNA allows mixing (reassortment
Reassortment
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...
) of the genes if more than one variety of influenza virus has infected the same cell (superinfection
Superinfection
In virology, superinfection is the process by which a cell, that has previously been infected by one virus, gets coinfected with a different strain of the virus, or another virus at a later point in time. Viral superinfections of serious conditions can lead to resistant strains of the virus, which...
). The resulting alteration in the genome segments packaged in to viral progeny confers new behavior, sometimes the ability to infect new host species or to overcome protective immunity of host populations to its old genome (in which case it is called an antigenic shift
Antigenic shift
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...
).
Viability and disinfection
Mammalian influenza virus tend to be labile, but can survive several hours in mucus. Avian influenza virus can survive for 100 days in distilled water at room temperature, and 200 days at 17 °C (62.6 °F). The avian virus is inactivated more quickly in manure, but can survive for up to 2 weeks in feces on cages. Avian influenza viruses can survive indefinitely when frozen. Influenza viruses are susceptible to bleach, 70% ethanol, aldehydes, oxidizing agents, and quaternary ammonium compounds. They are inactivated by heat of 133 °F (56.1 °C) for minimum of 60 minutes, as well as by low pH <2.Vaccination and Prophylaxis
Vaccines and drugs are, however, available for the prophylaxis and treatment of influenza virus infections. Vaccines are composed of either inactivated or live attenuated virions of the H1N1 and H3N2 human influenza A viruses as well as those of influenza B viruses. Because the antigenicities of the wild viruses evolve, vaccines are reformulated annually by updating the seed strains.However, when the antigenicities of the seed strains and wild viruses do not match, vaccines fail to protect the vaccinees. In addition, even when they do match, escape mutants are often generated. The drugs include amantadine, which inhibits the uncoating of virions by interfering with M2, and oseltamivir (marketed under the brand name Tamiflu), which inhibits the release of virions from infected cells by interfering with NA. However, escape mutants are often generated for the former drug and less frequently for the latter drug.
External links
- Health-EU Portal EU work to prepare a global response to influenza.
- Influenza Research Database Database of influenza genomic sequences and related information.
- Swine Flu News (World View) Swine Flu News (World View)
- European Commission - Public Health EU coordination on Pandemic (H1N1) 2009