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__NOTOC__
{{Influenza}}
{{Influenza}}
'''For more information about non-human (variant) influenza viruses that may be transmitted to humans, see [[Zoonotic influenza]]'''<br><br>
{{CMG}}; {{AE}} {{AL}}
==Overview==
Influenza infection is caused by the influenza virus that belong to the family [[Orthomyxoviridae]].  Three types of influenza virus  have been reported to cause clinical illness in humans: types A, B, and C.  Influenza virus can be found in humans, as well as in poultry, pigs, and bats.


'''For patient information click [[Influenza (patient information)|here]]'''
==Taxonomy==
'''''Viruses; ssRNA viruses; ssRNA negative-strand viruses; Orthomyxoviridae; Influenzavirus A; Influenza A virus'''''<ref name=Tx>>{{cite web | title = Taxonomy browser (Influenzavirus) | url = http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Undef&id=11308&lvl=3&keep=1&srchmode=1&unlock}}</ref><br>
'''''Viruses; ssRNA viruses; ssRNA negative-strand viruses; Orthomyxoviridae; Influenzavirus B; Influenza B virus'''''<ref name=Tx>{{cite web | title = Taxonomy browser (Influenzavirus) | url = http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Undef&id=11308&lvl=3&keep=1&srchmode=1&unlock}}</ref><br>
'''''Viruses; ssRNA viruses; ssRNA negative-strand viruses; Orthomyxoviridae; Influenzavirus C; Influenza C virus'''''<ref name=Tx>{{cite web | title = Taxonomy browser (Influenzavirus) | url = http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Undef&id=11308&lvl=3&keep=1&srchmode=1&unlock}}</ref><br>


{{CMG}}
*Orthomyxoviridae
:*'''Influenzavirus A'''
::*Influenza A virus
:::*(many subtypes)
:*'''Influenzavirus B'''
::*Influenza B virus
:::*(many subtypes)
:*'''Influenzavirus C'''
::*Influenza C virus
:::*(many subtypes)


==Overview==
*The international naming convention for influenza viruses uses the following components to name the virus:<ref name=CDC>{{cite web|url=http://www.cdc.gov/flu/about/viruses/types.htm| title=CDC Types of Influenza Viruses}}</ref>
'''Influenza''', commonly known as '''flu''', is an [[infectious disease]] of birds and [[mammal]]s caused by  [[RNA virus]]es of the biological family [[Orthomyxoviridae]] (the influenza viruses). In humans, common symptoms of influenza infection are [[fever]], [[pharyngitis|sore throat]], [[myalgia|muscle pains]], severe [[headache]], [[cough]]ing, [[fatigue (medical)|weakness]] and [[malaise|general discomfort]].
:*The antigenic type (A, B, C)
{{H5N1}}{{further|[[Influenzavirus A]], [[H5N1]] and [[Transmission and infection of H5N1]]}}
:*The host of origin (Swine, equine, chicken, etc. For human-origin viruses, no host of origin designation is given.)
==Infection in other animals==
:*Geographical origin (e.g., Hong Kong, Denver, Taiwan)
Influenza infects many animal species and transfer of viral strains between species can occur. Birds are thought to be the main [[host (biology)|animal reservoir]]s of influenza viruses.<ref>{{cite journal | author = Gorman O, Bean W, Kawaoka Y, Webster R | title = Evolution of the nucleoprotein gene of influenza A virus. | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=2319644 | journal = J Virol | volume = 64 | issue = 4 | pages = 1487–97 | year = 1990 | id = PMID 2319644}}</ref> Sixteen forms of [[hemagglutinin]] and 9 forms of [[neuraminidase]] have been identified. All known subtypes (HxNy) are found in birds but many subtypes are endemic in humans, dogs, horses, and pigs; populations of camels, ferrets, cats, seals, mink, and whales also show evidence of prior infection or exposure to influenza. Variants of flu virus are sometimes named according to the species the strain is endemic in or adapted to. The main variants named using this convention are: Bird flu, [[Human flu|Human Flu]], Swine Flu, Horse Flu and Dog Flu. (Cat flu generally refers to Feline viral rhinotracheitis or Feline calicivirus and not infection from an influenza virus.) In pigs, horses and dogs, influenza symptoms are similar to humans, with cough, fever and loss of appetite.<ref name=webster/> The frequency of animal diseases are not as well-studied as human infection, but an outbreak of influenza in harbour seals caused approximately 500 seal deaths off the New England coast in 1979–1980.<ref>{{cite journal | author = Hinshaw V, Bean W, Webster R, Rehg J, Fiorelli P, Early G, Geraci J, St Aubin D | title = Are seals frequently infected with avian influenza viruses? | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=6471169 | journal = J Virol | volume = 51 | issue = 3 | pages = 863-5 | year = 1984 | id = PMID 6471169}}</ref> On the other hand, outbreaks in pigs are common and do not cause severe mortality.<ref name=webster/>
:*Strain number (e.g., 15, 7)
:*Year of isolation (e.g., 57, 2009)
:*For influenza A viruses, the hemagglutinin and neuraminidase antigen description in parentheses (e.g.,(H1N1), (H5N1)).
 
===Influenza A===
*Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: the hemagglutinin (H) and the neuraminidase (N).
*There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes. (H1 through H18 and N1 through N11 respectively.)
*Influenza A viruses can be further broken down into different strains.
*Current subtypes of influenza A viruses found in people are influenza A (H1N1) and influenza A (H3N2) viruses.  
*In the spring of 2009, a new influenza A (H1N1) virus (CDC 2009 H1N1 Flu website) emerged to cause illness in people.
*This virus was very different from the human influenza A (H1N1) viruses circulating at that time.
*The new virus caused the first influenza pandemic in more than 40 years.
*That virus (often called “2009 H1N1”) has now replaced the H1N1 virus that was previously circulating in humans.
 
===Influenza B===
*Influenza B viruses are not divided into subtypes, but can be further broken down into lineages and strains.
*Currently circulating influenza B viruses belong to one of two lineages: B/Yamagata and B/Victoria.
<br>
{{further|[[Influenza classification]]}}
 
==Structure==
{|style="float:right"
|[[Image:Influenza virus structure.jpg|thumb|420px|Image courtesy of CDC[http://www.cdc.gov/flu/images/virus/fluvirus-antigentic-characterization-large-with-caption.jpg]]]
|}
* Influenza viruses (A, B and C) are very similar in overall structure, they arre single-stranded, enveloped, negative-sense RNA viruses.
* Influenza virus replicate inside the nucleus of the host-cell.
*The virus particle is 80–120 [[nanometre|nanometers]] in diameter and usually roughly spherical, although filamentous forms can occur.<ref>{{cite web|author=International Committee on Taxonomy of Viruses |title=The Universal Virus Database, version 4: Influenza A|url=http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/00.046.0.01.htm}}</ref><ref name=Lamb>{{cite journal|author=Lamb RA, Choppin PW |title=The gene structure and replication of influenza virus |journal=Annu. Rev. Biochem. |volume=52|issue=|pages=467–506 |year=1983 |pmid=6351727 |doi=10.1146/annurev.bi.52.070183.002343}}</ref>  
*These filamentous forms are more common in influenza C, which can form cordlike structures up to 500&nbsp;[[micrometre|micrometers]] long on the surfaces of infected cells.
*The [[viral envelope]] contains two main types of [[glycoprotein]]s, wrapped around a central core.
*The central core contains the viral [[RNA]] [[genome]] and other viral proteins that package and protect this RNA.  
*RNA tends to be single stranded but in special cases it is double.<ref name=Lamb/> Unusually for a virus, its genome is not a single piece of [[nucleic acid]]; instead, it contains seven or eight pieces of segmented [[negative-sense]] RNA, each piece of RNA containing either one or two [[gene]]s, which code for a gene product (protein).
*The influenza A genome contains 11 genes on eight pieces of RNA, encoding for 11 [[protein]]s: [[hemagglutinin]] (HA), [[neuraminidase]] (NA), [[nucleoprotein]] (NP), [[M1 protein|M1]], [[M2 protein|M2]], [[NS1 Influenza Protein|NS1]], NS2(NEP: nuclear export protein), PA, PB1 (polymerase basic 1), PB1-F2 and PB2.<ref name=Ghedin>{{cite journal |last=Ghedin |first=E | last2 = Sengamalay | first2 = NA | last3 = Shumway | first3 = M | last4 = Zaborsky | first4 = J | last5 = Feldblyum | first5 = T | last6 = Subbu | first6 = V | last7 = Spiro | first7 = DJ | last8 = Sitz | first8 = J | last9 = Koo | first9 = H |title=Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution |journal=[[Nature (journal)|Nature]] |volume=437 |issue=7062 |pages=1162–6 |date=October 2005 |pmid=16208317|doi=10.1038/nature04239 | bibcode=2005Natur.437.1162G}}</ref>
*Hemagglutinin (HA) and neuraminidase (NA) are the two large glycoproteins on the outside of the viral particles.
*HA is a [[lectin]] that mediates binding of the virus to target cells and entry of the viral genome into the target cell, while NA is involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles.<ref>{{cite journal |last=Suzuki |first=Y|title=Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses|url=http://www.jstage.jst.go.jp/article/bpb/28/3/399/_pdf |journal=Biol Pharm Bull |volume=28 |issue=3 |pages=399–408 |year=2005|pmid=15744059 |doi=10.1248/bpb.28.399}}</ref>  
*These proteins are targets for [[antiviral drugs]]<ref>{{cite journal|last=Wilson |first=J |author2=von Itzstein M |title=Recent strategies in the search for new anti-influenza therapies |journal=Curr Drug Targets |volume=4 |issue=5 |pages=389–408 |date=July 2003 |pmid=12816348 |doi=10.2174/1389450033491019}}</ref> and [[antigen]]s to which [[antibodies]] can be raised.


Flu symptoms in birds are variable and can be unspecific.<ref>{{cite journal | author = Elbers A, Koch G, Bouma A | title = Performance of clinical signs in poultry for the detection of outbreaks during the avian influenza A (H7N7) epidemic in The Netherlands in 2003. | journal = Avian Pathol | volume = 34 | issue = 3 | pages = 181-7 | year = 2005 | id = PMID 16191700}}</ref> The symptoms following infection with low-pathogenicity avian influenza may be as mild as ruffled feathers, a small reduction in egg production, or weight loss combined with minor respiratory disease.<ref>Capua I, Mutinelli F. "Low pathogenicity (LPAI) and highly pathogenic (HPAI) avian influenza in turkeys and chicken." In: Capua I, Mutinelli F. (eds.), A Colour Atlas and Text on Avian Influenza, Papi Editore, Bologna, 2001, pp. 13–20</ref> Since these mild symptoms can make diagnosis in the field difficult, tracking the spread of avian influenza requires laboratory testing of samples from infected birds. Some strains such as Asian [[H9N2]] are highly virulent to poultry, and may cause more extreme symptoms and significant mortality.<ref>{{cite journal | author = Bano S, Naeem K, Malik S | title = Evaluation of pathogenic potential of avian influenza virus serotype H9N2 in chickens. | journal = Avian Dis | volume = 47 | issue = 3 Suppl | pages = 817-22 | year = 2003 | id = PMID 14575070}}</ref> In its most highly pathogenic form, influenza in chickens and turkeys produces a sudden appearance of severe symptoms and almost 100% mortality within two days.<ref>{{cite journal | author = Swayne D, Suarez D | title = Highly pathogenic avian influenza. | journal = Rev Sci Tech | volume = 19 | issue = 2 | pages = 463-82 | year = 2000 | id = PMID 10935274}}</ref> As the virus spreads rapidly in the crowded conditions seen in the intensive farming of chickens and turkeys, these outbreaks can cause large economic losses to poultry farmers.
==Tropism==
*The viruses attach to cells within the nasal passages and throat in the respiratory tract.  
*The influenza virus’s hemagglutinin (HA) surface proteins then bind to the sialic acid receptors on the surface of a human respiratory tract cell.  
*The structure of the influenza virus’s HA surface proteins is designed to fit the sialic acid receptors of the human cell, like a key to a lock.  
*Once the key enters the lock, the influenza virus is then able to enter and infect the cell. This marks the beginning of a flu infection


An avian-adapted, highly pathogenic strain of H5N1 (called HPAI A(H5N1), for "highly pathogenic avian influenza virus of type A of subtype H5N1") causes [[transmission and infection of H5N1|H5N1 flu]], commonly known as "avian influenza" or simply "bird flu", and is [[endemic (epidemiology)|endemic]] in many bird populations, especially in Southeast Asia. This Asian lineage strain of HPAI A(H5N1) is [[global spread of H5N1|spreading globally]]. It is [[epizootic]] (an epidemic in non-humans) and panzootic (a disease affecting animals of many species, especially over a wide area) killing tens of millions of birds and spurring the culling of hundreds of millions of other birds in an attempt to control its spread. Most references in the media to "bird flu" and most references to H5N1 are about this specific strain.<ref>{{cite journal | author = Li K, Guan Y, Wang J, Smith G, Xu K, Duan L, Rahardjo A, Puthavathana P, Buranathai C, Nguyen T, Estoepangestie A, Chaisingh A, Auewarakul P, Long H, Hanh N, Webby R, Poon L, Chen H, Shortridge K, Yuen K, Webster R, Peiris J | title = Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. | journal = Nature | volume = 430 | issue = 6996 | pages = 209-13 | year = 2004 | id = PMID 15241415}}</ref><ref>Li KS, Guan Y, Wang J, Smith GJ, Xu KM, Duan L, Rahardjo AP, Puthavathana P, Buranathai C, Nguyen TD, Estoepangestie AT, Chaisingh A, Auewarakul P, Long HT, Hanh NT, Webby RJ, Poon LL, Chen H, Shortridge KF, Yuen KY, Webster RG, Peiris JS. [http://darwin.nap.edu/books/0309095042/html/116.html "The Threat of Pandemic Influenza: Are We Ready?" Workshop Summary] The National Academies Press (2005) "Today's Pandemic Threat: Genesis of a Highly Pathogenic and Potentially Pandemic H5N1 Influenza Virus in Eastern Asia", pages 116–130</ref>
==Natural Reservoir==
{| style="border: 0px; font-size: 85%; margin: 3px; width:400px; float:right"
|valign=top|
|+<small>'''Influenza A subtypes and the species in which they have been detected'''</small>
! style="background: #4479BA; color:#FFF;  width: 200px;" | Species
! style="background: #4479BA; color:#FFF;  width: 200px;" | Hemagglutinin <BR>Subtypes
! style="background: #4479BA; color:#FFF;  width: 200px;" | Neuraminidase <BR>Subtypes
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | Humans
| style="padding: 5px 5px; background: #F5F5F5;" | H1, H2, H3, H5, H6, H7, H9, H10
| style="padding: 5px 5px; background: #F5F5F5;" | N1, N2, N6, N7, N8, N9
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | Poultry
| style="padding: 5px 5px; background: #F5F5F5;" | H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16
| style="padding: 5px 5px; background: #F5F5F5;" | N1, N2, N3, N4, N5, N6, N7, N8, N9
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | Pigs
| style="padding: 5px 5px; background: #F5F5F5;" | H1, H2, H3, H4, H5, H9
| style="padding: 5px 5px; background: #F5F5F5;" | N1, N2
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | Bats
| style="padding: 5px 5px; background: #F5F5F5;" | H17, H18
| style="padding: 5px 5px; background: #F5F5F5;" | N10, N11
|-
| style="padding: 0px 5px; background: #F5F5F5;" colspan=3| <small>'''Adapted from CDC''' <ref name="CDC Transmission">{{cite web|url=http://www.cdc.gov/flu/about/viruses/transmission.htm#subtypes| title=CDC Seasonal Influenza - Transmission of Influenza Viruses from Animals to People}} </ref></small>
|}
*In nature, the flu virus is found in wild aquatic birds, such as ducks and shore birds.
* It has persisted in these birds for millions of years and does not typically harm them; but the frequently mutating flu viruses can readily jump the species barrier from wild birds to domesticated poultry and swine.
*Pigs can be infected by both bird (avian) flu and the form that infects humans.
*In a setting such as a farm where chickens, pigs, and humans live in close proximity, pigs act as an influenza virus mixing bowl.
*If a pig is infected with avian and human flu simultaneously, the two types of virus may exchange genes.
*Such a "reassorted" flu virus can sometimes spread from pigs to people.
*Depending on the combination of avian flu proteins that make it into the human population, the flu may be more or less severe.
*In 1997, for the first time, scientists found that a form of avian H5N1 flu skipped the pig step and infected humans directly.
*Alarmed health officials feared a worldwide epidemic (a pandemic), but fortunately, the virus could not pass from person to person and thus did not spark an epidemic.


At present, HPAI A(H5N1) is an avian disease and there is no evidence suggesting efficient human-to-human transmission of HPAI A(H5N1). In almost all cases, those infected have had extensive physical contact with infected birds.<ref>{{cite journal | author = Liu J | title = Avian influenza—a pandemic waiting to happen? | url=http://jmii.org/content/pdf/v39n1p4.pdf | journal = J Microbiol Immunol Infect | volume = 39 | issue = 1 | pages = 4–10 | year = 2006 | id = PMID 16440117}}</ref> In the future, H5N1 may mutate or reassort into a strain capable of efficient human-to-human transmission. Due to its high lethality and [[virulence]], its [[endemic (epidemiology)|endemic]] presence, and its large and increasing biological host reservoir, the H5N1 virus is the world's pandemic threat in the 2006–7 flu season, and billions of dollars are being raised and spent researching H5N1 and preparing for a potential [[influenza pandemic]].<ref name=Rosenthal> Rosenthal, E. and Bradsher, K. [http://www.nytimes.com/2006/03/16/business/16bird.html?_r=1&oref=slogin Is Business Ready for a Flu Pandemic?] The New York Times 16-03-2006 Accessed 17-04-2006</ref>
==Microscopic Pathology==
<gallery>
Image:Electron Micrograph Images of H7N9 Virus from China.jpg|Electron Micrograph Images of H7N9 Virus from China. <br> <small>Image obtained from CDC.</small>
Image:Influenza Virus.jpg|Produced by the National Institute of Allergy and Infectious Diseases (NIAID), this digitally-colorized transmission electron micrograph (TEM) depicts numbers of H1N1 influenza virus particles. Surface proteins located on the surface of the virus particles are shown in black. <br> <small>Image obtained from Public Health Image Library (PHIL).</small>
Image:Influenza A (H7N9) virus.jpg |This negatively-stained transmission electron micrograph (TEM) captured some of the ultrastructural details exhibited by the new influenza A (H7N9) virus.<br> <small>Image obtained from Public Health Image Library (PHIL).</small>
Image:Novel H1N1 virus virions.jpg| This colorized transmission electron micrograph (TEM) revealed the presence of a number of Novel H1N1 virus virions in this tissue culture sample.<br> <small>Image obtained from Public Health Image Library (PHIL).</small>
Image:H3N2 subtype of the influenza A virus.jpg|This negatively-stained transmission electron micrograph (TEM) revealed the presence of a number of Hong Kong flu virus virions, the H3N2 subtype of the influenza A virus.<br> <small>Image obtained from Public Health Image Library (PHIL).</small>
</gallery>


==References==
==References==
{{reflist|2}}
{{Reflist|2}}
{{WH}}
{{WS}}


[[Category:Disease]]
[[Category:Disease]]
[[Category:Mature chapter]]
[[Category:Pulmonology]]
[[Category:Pulmonology]]
[[Category:Influenza| ]]
[[Category:Influenza| ]]
[[Category:Infectious disease]]
[[Category:H5N1]]
 
[[Category:Orthomyxoviridae]]
{{WH}}
{{WS}}

Latest revision as of 22:24, 29 July 2020

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For more information about non-human (variant) influenza viruses that may be transmitted to humans, see Zoonotic influenza

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [3]

Overview

Influenza infection is caused by the influenza virus that belong to the family Orthomyxoviridae. Three types of influenza virus have been reported to cause clinical illness in humans: types A, B, and C. Influenza virus can be found in humans, as well as in poultry, pigs, and bats.

Taxonomy

Viruses; ssRNA viruses; ssRNA negative-strand viruses; Orthomyxoviridae; Influenzavirus A; Influenza A virus[1]
Viruses; ssRNA viruses; ssRNA negative-strand viruses; Orthomyxoviridae; Influenzavirus B; Influenza B virus[1]
Viruses; ssRNA viruses; ssRNA negative-strand viruses; Orthomyxoviridae; Influenzavirus C; Influenza C virus[1]

  • Orthomyxoviridae
  • Influenzavirus A
  • Influenza A virus
  • (many subtypes)
  • Influenzavirus B
  • Influenza B virus
  • (many subtypes)
  • Influenzavirus C
  • Influenza C virus
  • (many subtypes)
  • The international naming convention for influenza viruses uses the following components to name the virus:[2]
  • The antigenic type (A, B, C)
  • The host of origin (Swine, equine, chicken, etc. For human-origin viruses, no host of origin designation is given.)
  • Geographical origin (e.g., Hong Kong, Denver, Taiwan)
  • Strain number (e.g., 15, 7)
  • Year of isolation (e.g., 57, 2009)
  • For influenza A viruses, the hemagglutinin and neuraminidase antigen description in parentheses (e.g.,(H1N1), (H5N1)).

Influenza A

  • Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: the hemagglutinin (H) and the neuraminidase (N).
  • There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes. (H1 through H18 and N1 through N11 respectively.)
  • Influenza A viruses can be further broken down into different strains.
  • Current subtypes of influenza A viruses found in people are influenza A (H1N1) and influenza A (H3N2) viruses.
  • In the spring of 2009, a new influenza A (H1N1) virus (CDC 2009 H1N1 Flu website) emerged to cause illness in people.
  • This virus was very different from the human influenza A (H1N1) viruses circulating at that time.
  • The new virus caused the first influenza pandemic in more than 40 years.
  • That virus (often called “2009 H1N1”) has now replaced the H1N1 virus that was previously circulating in humans.

Influenza B

  • Influenza B viruses are not divided into subtypes, but can be further broken down into lineages and strains.
  • Currently circulating influenza B viruses belong to one of two lineages: B/Yamagata and B/Victoria.


Further information: [[:Influenza classification]]

Structure

Image courtesy of CDC[1]
  • Influenza viruses (A, B and C) are very similar in overall structure, they arre single-stranded, enveloped, negative-sense RNA viruses.
  • Influenza virus replicate inside the nucleus of the host-cell.
  • The virus particle is 80–120 nanometers in diameter and usually roughly spherical, although filamentous forms can occur.[3][4]
  • These filamentous forms are more common in influenza C, which can form cordlike structures up to 500 micrometers long on the surfaces of infected cells.
  • The viral envelope contains two main types of glycoproteins, wrapped around a central core.
  • The central core contains the viral RNA genome and other viral proteins that package and protect this RNA.
  • RNA tends to be single stranded but in special cases it is double.[4] Unusually for a virus, its genome is not a single piece of nucleic acid; instead, it contains seven or eight pieces of segmented negative-sense RNA, each piece of RNA containing either one or two genes, which code for a gene product (protein).
  • The influenza A genome contains 11 genes on eight pieces of RNA, encoding for 11 proteins: hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), M1, M2, NS1, NS2(NEP: nuclear export protein), PA, PB1 (polymerase basic 1), PB1-F2 and PB2.[5]
  • Hemagglutinin (HA) and neuraminidase (NA) are the two large glycoproteins on the outside of the viral particles.
  • HA is a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell, while NA is involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles.[6]
  • These proteins are targets for antiviral drugs[7] and antigens to which antibodies can be raised.

Tropism

  • The viruses attach to cells within the nasal passages and throat in the respiratory tract.
  • The influenza virus’s hemagglutinin (HA) surface proteins then bind to the sialic acid receptors on the surface of a human respiratory tract cell.
  • The structure of the influenza virus’s HA surface proteins is designed to fit the sialic acid receptors of the human cell, like a key to a lock.
  • Once the key enters the lock, the influenza virus is then able to enter and infect the cell. This marks the beginning of a flu infection

Natural Reservoir

Influenza A subtypes and the species in which they have been detected
Species Hemagglutinin
Subtypes 		Neuraminidase
Subtypes
Humans H1, H2, H3, H5, H6, H7, H9, H10 N1, N2, N6, N7, N8, N9
Poultry H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16 N1, N2, N3, N4, N5, N6, N7, N8, N9
Pigs H1, H2, H3, H4, H5, H9 N1, N2
Bats H17, H18 N10, N11
Adapted from CDC [8]
  • In nature, the flu virus is found in wild aquatic birds, such as ducks and shore birds.
  • It has persisted in these birds for millions of years and does not typically harm them; but the frequently mutating flu viruses can readily jump the species barrier from wild birds to domesticated poultry and swine.
  • Pigs can be infected by both bird (avian) flu and the form that infects humans.
  • In a setting such as a farm where chickens, pigs, and humans live in close proximity, pigs act as an influenza virus mixing bowl.
  • If a pig is infected with avian and human flu simultaneously, the two types of virus may exchange genes.
  • Such a "reassorted" flu virus can sometimes spread from pigs to people.
  • Depending on the combination of avian flu proteins that make it into the human population, the flu may be more or less severe.
  • In 1997, for the first time, scientists found that a form of avian H5N1 flu skipped the pig step and infected humans directly.
  • Alarmed health officials feared a worldwide epidemic (a pandemic), but fortunately, the virus could not pass from person to person and thus did not spark an epidemic.

Microscopic Pathology

  • Electron Micrograph Images of H7N9 Virus from China. Image obtained from CDC.

    Electron Micrograph Images of H7N9 Virus from China.
    Image obtained from CDC.

  • Produced by the National Institute of Allergy and Infectious Diseases (NIAID), this digitally-colorized transmission electron micrograph (TEM) depicts numbers of H1N1 influenza virus particles. Surface proteins located on the surface of the virus particles are shown in black. Image obtained from Public Health Image Library (PHIL).

    Produced by the National Institute of Allergy and Infectious Diseases (NIAID), this digitally-colorized transmission electron micrograph (TEM) depicts numbers of H1N1 influenza virus particles. Surface proteins located on the surface of the virus particles are shown in black.
    Image obtained from Public Health Image Library (PHIL).

  • This negatively-stained transmission electron micrograph (TEM) captured some of the ultrastructural details exhibited by the new influenza A (H7N9) virus. Image obtained from Public Health Image Library (PHIL).

    This negatively-stained transmission electron micrograph (TEM) captured some of the ultrastructural details exhibited by the new influenza A (H7N9) virus.
    Image obtained from Public Health Image Library (PHIL).

  • This colorized transmission electron micrograph (TEM) revealed the presence of a number of Novel H1N1 virus virions in this tissue culture sample. Image obtained from Public Health Image Library (PHIL).

    This colorized transmission electron micrograph (TEM) revealed the presence of a number of Novel H1N1 virus virions in this tissue culture sample.
    Image obtained from Public Health Image Library (PHIL).

  • This negatively-stained transmission electron micrograph (TEM) revealed the presence of a number of Hong Kong flu virus virions, the H3N2 subtype of the influenza A virus. Image obtained from Public Health Image Library (PHIL).

    This negatively-stained transmission electron micrograph (TEM) revealed the presence of a number of Hong Kong flu virus virions, the H3N2 subtype of the influenza A virus.
    Image obtained from Public Health Image Library (PHIL).

References

  1. ↑ 1.0 1.1 1.2 >"Taxonomy browser (Influenzavirus)".
  2. ↑ "CDC Types of Influenza Viruses".
  3. ↑ International Committee on Taxonomy of Viruses. "The Universal Virus Database, version 4: Influenza A".
  4. ↑ 4.0 4.1 Lamb RA, Choppin PW (1983). "The gene structure and replication of influenza virus". Annu. Rev. Biochem. 52: 467–506. doi:10.1146/annurev.bi.52.070183.002343. PMID 6351727.
  5. ↑ Ghedin, E; Sengamalay, NA; Shumway, M; Zaborsky, J; Feldblyum, T; Subbu, V; Spiro, DJ; Sitz, J; Koo, H (October 2005). "Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution". Nature. 437 (7062): 1162–6. Bibcode:2005Natur.437.1162G. doi:10.1038/nature04239. PMID 16208317.
  6. ↑ Suzuki, Y (2005). "Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses". Biol Pharm Bull. 28 (3): 399–408. doi:10.1248/bpb.28.399. PMID 15744059.
  7. ↑ Wilson, J; von Itzstein M (July 2003). "Recent strategies in the search for new anti-influenza therapies". Curr Drug Targets. 4 (5): 389–408. doi:10.2174/1389450033491019. PMID 12816348.
  8. ↑ "CDC Seasonal Influenza - Transmission of Influenza Viruses from Animals to People".

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