Orthomyxoviridae

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This article is about the virus family that contains seven genera. For specific information about the subfamily that affects humans, see Influenza.
Orthomyxoviridae
Influenza A and influenza B viruses genome, mRNA, and virion diagram
Virus classification Edit this classification
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum:
Negarnaviricota
Class: Insthoviricetes
Order: Articulavirales
Family: Orthomyxoviridae
Genera

Orthomyxoviridae (from

Isavirus, Thogotovirus, and Quaranjavirus. The first four genera contain viruses that cause influenza in birds (see also avian influenza) and mammals, including humans. Isaviruses infect salmon; the thogotoviruses are arboviruses, infecting vertebrates and invertebrates (such as ticks and mosquitoes).[2][3][4] The Quaranjaviruses are also arboviruses, infecting vertebrates (birds) and invertebrates (arthropods
).

The four genera of Influenza virus that infect vertebrates, which are identified by antigenic differences in their

matrix protein
, are as follows:

Structure

Influenza A virus structure

The influenzavirus

nm in diameter, or filamentous with particles 80–100 nm in diameter and up to 20 µm long.[5] There are approximately 500 distinct spike-like surface projections in the envelope each projecting 10–14 nm from the surface with varying surface densities. The major glycoprotein (HA) spike is interposed irregularly by clusters of neuraminidase (NA) spikes, with a ratio of HA to NA of about 10 to 1.[6]

The viral envelope composed of a

nucleocapsids; nucleoproteins of different size classes with a loop at each end; the arrangement within the virion is uncertain. The ribonuclear proteins are filamentous and fall in the range of 50–130 nm long and 9–15 nm in diameter with helical symmetry.[citation needed
]

Genome

For an in-depth example, see H5N1 genetic structure.
Influenzavirus genomes. Segments translate to polymerase (PB1, PB2, and PA), hemagglutinin (HA), neuramindase (NA), nucleoprotein (NP), membrane protein (M), and non-structural protein (NS).

Viruses of the family Orthomyxoviridae contain six to eight segments of linear negative-sense single stranded RNA. They have a total genome length that is 10,000–14,600 nucleotides (nt).[7] The influenza A genome, for instance, has eight pieces of segmented negative-sense RNA (13.5 kilobases total).[8]

The best-characterised of the influenzavirus proteins are hemagglutinin and neuraminidase, two large glycoproteins found on the outside of the viral particles. Hemagglutinin is a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell.[9] In contrast, neuraminidase is an enzyme involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles. The hemagglutinin (H) and neuraminidase (N) proteins are key targets for antibodies and antiviral drugs,[10][11] and they are used to classify the different serotypes of influenza A viruses, hence the H and N in H5N1.

The 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. In Influenza A (H1N1) PB1-F2 is produced from an alternative reading frame in PB1. The M and NS genes produce two different genes via alternative splicing.[12]

Replication cycle

Infection and replication of the influenza virus. The steps in this process are discussed in the text.

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. Out of a host, 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 detergents.[13][14][15]

The viruses bind to a cell through interactions between its

mRNA and using the released nucleotides for vRNA synthesis and also inhibiting translation of host-cell mRNAs.[19]

Negative-sense vRNAs that form the genomes 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).[20] 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.[16] After the release of new influenza virus, the host cell dies.

Transcription of mRNAs initiated by viral polymerase using cap snatching

Orthomyxoviridae viruses are one of two RNA viruses that replicate in the nucleus (the other being

retroviridae). This is because the machinery of orthomyxo viruses cannot make their own mRNAs. They use cellular RNAs as primers for initiating the viral mRNA synthesis in a process known as cap snatching.[21] Once in the nucleus, the RNA Polymerase Protein PB2 finds a cellular pre-mRNA and binds to its 5′ capped end. Then RNA Polymerase PA cleaves off the cellular mRNA near the 5′ end and uses this capped fragment as a primer for transcribing the rest of the viral RNA genome in viral mRNA.[22] This is due to the need of mRNA to have a 5′ cap in order to be recognized by the cell's ribosome
for translation.

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.[23] 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 into 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).[10]

Classification

In a

phylogenetic-based taxonomy, the category RNA virus includes the subcategory negative-sense ssRNA virus, which includes the order Articulavirales, and the family Orthomyxoviridae. The genera-associated species and serotypes
of Orthomyxoviridae are shown in the following table.

Orthomyxovirus Genera, Species, and Serotypes
Genus Species (* indicates type species)
Serotypes
or Subtypes 		Hosts
Alphainfluenzavirus Influenza A virus*
H10N7
 Human, pig, bird, horse, bat
Betainfluenzavirus
Influenza B virus
* 		Victoria, Yamagata[24] Human, seal
Gammainfluenzavirus
Influenza C virus
* 		Human, pig
Deltainfluenzavirus
Influenza D virus
* 		Pig, cattle
Isavirus
Infectious salmon anemia virus
* 		Atlantic salmon
Thogotovirus Thogotovirus* Tick, mosquito, mammal (including human)
Dhori virus
Batken virus, Bourbon virus, Jos virus
Quaranjavirus[25]
Quaranfil virus,* Johnston Atoll virus

Types

There are four genera of influenza virus, each containing only a single species, or type. Influenza A and C infect a variety of species (including humans), while influenza B almost exclusively infects humans, and influenza D infects cattle and pigs.[26][27][28]

Influenza A

Main article: Influenza A virus
Diagram of influenza nomenclature

Influenza A viruses are further classified, based on the viral surface proteins hemagglutinin (HA or H) and neuraminidase (NA or N). 18 HA subtypes (or serotypes) and 11 NA subtypes of influenza A virus have been isolated in nature. Among these, the HA subtype 1-16 and NA subtype 1-9 are found in wild waterfowl and shorebirds and the HA subtypes 17-18 and NA subtypes 10-11 have only been isolated from bats.[29][30]

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.[31][32]

Examples of the nomenclature are:

  1. A/Brisbane/59/2007 (H1N1)
  2. A/Moscow/10/99 (H3N2).

The type A influenza viruses are the most virulent human pathogens among the three influenza types and cause the most severe disease. It is thought that all influenza A viruses causing outbreaks or pandemics originate from wild aquatic birds.

humans
, ordered by the number of confirmed human deaths, are:

Known
flu pandemics[10][39][40]
Name of pandemic Date Deaths Case fatality rate Subtype involved
Pandemic Severity Index
1889–1890 flu pandemic
(Asiatic or Russian Flu)[41]
 1889–1890 1 million 0.15% Possibly
H2N2
 —
1918 flu pandemic
(Spanish flu)[42]
 1918–1920 20 to 100 million 2%
H1N1
 5
Asian Flu
 1957–1958 1 to 1.5 million 0.13%
H2N2
 2
Hong Kong Flu
 1968–1969 0.75 to 1 million <0.1%
H3N2
 2
Russian flu 1977–1978 No accurate count —
H1N1
 —
2009 flu pandemic[43][44]
 2009–2010 105,700–395,600[45] 0.03%
H1N1
 N/A

Influenza B

Main article: Influenza B virus
Host range of influenza viruses

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 seal.[46] This type of influenza mutates at a rate 2–3 times lower than type A[47] and consequently is less genetically diverse, with only one influenza B serotype.[26] As a result of this lack of antigenic 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.[48] 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.[49]

Influenza C

Main article: Influenza C virus

The influenza C virus infects humans and pigs, and can cause severe illness and local epidemics.[50] However, influenza C is less common than the other types and usually causes mild disease in children.[51][52]

Influenza D

Main article: Influenza D virus

This is a genus that was classified in 2016, the members of which were first isolated in 2011.[53] This genus appears to be most closely related to Influenza C, from which it diverged several hundred years ago.[54] There are at least two extant strains of this genus.[55] The main hosts appear to be cattle, but the virus has been known to infect pigs as well.

Viability and disinfection

Mammalian influenza viruses tend to be labile, but can survive several hours in mucus.[56] Avian influenza virus can survive for 100 days in distilled water at room temperature, and 200 days at 17 °C (63 °F). The avian virus is inactivated more quickly in manure, but can survive for up to two weeks in feces on cages. Avian influenza viruses can survive indefinitely when frozen.[56] Influenza viruses are susceptible to bleach, 70% ethanol, aldehydes, oxidizing agents, and quaternary ammonium compounds. They are inactivated by heat of 133 °F (56 °C) for minimum of 60 minutes, as well as by low pH <2.[56]

Vaccination and prophylaxis

Targets of anti-influenza agents that are licensed or under investigation

Vaccines and drugs are 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.[citation needed]

When the antigenicities of the seed strains and wild viruses do not match, vaccines fail to protect the vaccinees.[citation needed] In addition, even when they do match, escape mutants are often generated.[citation needed]

Drugs available for the treatment of influenza include

Tamiflu), Zanamivir, and Peramivir, which inhibit 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.[57]

See also

References

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Further reading

External links

Wikispecies has information related to Orthomyxoviridae.