Influenza causes: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Bot: Removing from Primary care)
 
(41 intermediate revisions by 3 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Influenza}}
{{Influenza}}
{{CMG}}  
'''For more information about non-human (variant) influenza viruses that may be transmitted to humans, see [[Zoonotic influenza]]'''<br><br>
{{CMG}}; {{AE}} {{AL}}
==Overview==
==Overview==
{{Flu}}{{H5N1}}
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==
==Taxonomy==
*There are three types of influenza viruses: A, B and C.
'''''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>
* Human influenza A and B viruses cause seasonal epidemics of disease almost every winter in the United States.  
'''''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>
*The emergence of a new and very different influenza virus to infect people can cause an influenza pandemic. Influenza type C infections cause a mild respiratory illness and are not thought to cause epidemics.
'''''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>
*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 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.


:*The antigenic type (e.g., A, B, C)
*Orthomyxoviridae
:*The host of origin (e.g., swine, equine, chicken, etc. For human-origin viruses, no host of origin designation is given.)
:*'''Influenzavirus A'''
:*Geographical origin (e.g., Denver, Taiwan, etc.)
::*Influenza A virus
:*Strain number (e.g., 15, 7, etc.)
:::*(many subtypes)
:*Year of isolation (e.g., 57, 2009, etc.)
:*'''Influenzavirus B'''
:*For influenza A viruses, the hemagglutinin and neuraminidase antigen description in parentheses (e.g., (H1N1), (H5N1)
::*Influenza B virus
:::*(many subtypes)
:*'''Influenzavirus C'''
::*Influenza C virus
:::*(many subtypes)


*Influenza A (H1N1), A (H3N2), and one or two influenza B viruses (depending on the vaccine) are included in each year’s influenza vaccine. Getting a flu vaccine can protect against flu viruses that are the same or related to the viruses in the vaccine. Information about this season’s vaccine can be found atPreventing Seasonal Flu with Vaccination. The seasonal flu vaccine does not protect against influenza C viruses. In addition, flu vaccines will NOT protect against infection and illness caused by other viruses that also can cause influenza-like symptoms. There are many other non-flu viruses that can result in influenza-like illness (ILI) that spread during flu season.
*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>
:*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)).


*Genetic factors in distinguishing between "[[human flu]] viruses" and "[[avian influenza]] viruses" include:
===Influenza A===
:'''PB2''': ([[RNA polymerase]]): [[Amino acid]] (or [[residue]]) position 627 in the PB2 protein encoded by the PB2 [[RNA]] gene. Until [[H5N1]], all known avian influenza viruses had a [[Glutamic acid|Glu]] at position 627, while all human influenza viruses had a [[lysine]].  
*Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: the hemagglutinin (H) and the neuraminidase (N).
:'''HA''': ([[hemagglutinin]]): Avian influenza HA bind alpha 2-3 [[sialic acid]] receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors.
*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 A==
===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]]}}


The Influenza A virus subtypes that have been confirmed in [[humans]], ordered by the number of known human pandemic deaths, are:
==Structure==
*[[H1N1]] caused "[[Spanish Flu]]"
{|style="float:right"
*[[H2N2]] caused "Asian Flu"
|[[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]]]
*[[H3N2]] caused "Hong Kong Flu"
|}
*[[H5N1]] is the world's major [[influenza pandemic]] threat
* Influenza viruses (A, B and C) are very similar in overall structure, they arre single-stranded, enveloped, negative-sense RNA viruses.
*[[H7N7]] has unusual [[zoonotic]] potential
* Influenza virus replicate inside the nucleus of the host-cell.
*[[H1N2]] is currently endemic in humans and pigs
*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>
*[[H9N2]], [[H7N2]], [[H7N3]], [[H10N7]].
*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.


;H1N1
==Tropism==
{{main|H1N1}}
*The viruses attach to cells within the nasal passages and throat in the respiratory tract.
:[[H1N1]] is currently endemic in both human and pig populations. A variant of [[H1N1]] was responsible for the [[Spanish flu]] [[pandemic]] that killed some 50 million to 100 million people worldwide over about a year in [[1918]] and [[1919]]. <ref>[http://www.nap.edu/books/0309095042/html/7.html NAP Books] National Academies Press Books - ''The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005)'' - page 7.</ref> Controversy arose in October, [[2005]], after the H1N1 [[genome]] was published in the journal, [[Science (journal)|''Science'']]. Many fear that this information could be used for [[bioterrorism]].
*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


:"When he compared the [[Spanish flu|1918 virus]] with today's human flu viruses, Dr. Taubenberger noticed that it had alterations in just 25 to 30 of the virus's 4,400 amino acids. Those few changes turned a bird virus into a killer that could spread from person to person." <ref>[http://www.nytimes.com/2005/11/08/science/08flu.html?pagewanted=2 New York Times] Published: November 8, 2005 - ''Hazard in Hunt for New Flu: Looking for Bugs in All the Wrong Places''</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.


;H2N2
==Microscopic Pathology==
{{main|H2N2}}
<gallery>
:The [[Asian Flu]] was a [[pandemic]] outbreak of [[H2N2]] avian influenza that originated in [[China]] in [[1957]], spread worldwide that same year during which a [[influenza vaccine]] was developed, lasted until [[1958]] and caused between one and four million deaths.
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>
;H3N2
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>
{{main|H3N2}}
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>
:[[H3N2]] is currently endemic in both human and pig populations. It evolved from [[H2N2]] by [[antigenic shift]] and caused the [[Hong Kong Flu]] pandemic of 1968 and 1969 that killed up to 750,000. <ref>Detailed chart of its evolution [http://www.eletrica.ufsj.edu.br/~nepomuceno/references/epidemiology/ear_eal02.pdf here] at PDF called ''Ecology and Evolution of the Flu''</ref> "An early-onset, severe form of influenza A [[H3N2]] made headlines when it claimed the lives of several children in the United States in late [[2003]]." <ref>[http://www.nap.edu/books/0309095042/html/115.html NAP Books] National Academies Press Books - ''The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005)'' - page 115 - "There is particular pressure to recognize and heed the lessons of past influenza pandemics in the shadow of the worrisome 2003–2004 flu season. An early-onset, severe form of influenza A [[H3N2]] made headlines when it claimed the lives of several children in the United States in late 2003. As a result, stronger than usual demand for annual flu inactivated vaccine outstripped the vaccine supply, of which 10 to 20 percent typically goes unused. Because statistics on pediatric flu deaths had not been collected previously, it is unknown if the 2003–2004 season witnessed a significant change in mortality patterns."</ref>
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>
:The dominant strain of annual flu in [[January 2006]] is [[H3N2]]. Measured resistance to the standard antiviral drugs [[amantadine]] and [[rimantadine]] in H3N2 has increased from 1% in [[1994]] to 12% in [[2003]] to 91% in [[2005]]. <ref>[http://www.reason.com/rb/rb101905.shtml Reason] [http://www.nytimes.com/2006/01/15/health/15drugs.html New York Times] ''This Season's Flu Virus Is Resistant to 2 Standard Drugs'' By Altman Published: January 15, 2006 </ref>
 
:"[C]ontemporary human [[H3N2]] influenza viruses are now endemic in pigs in southern China and can reassort with avian [[H5N1]] viruses in this intermediate host." <ref>[http://www.nap.edu/books/0309095042/html/126.html NAP Books] National Academies Press Books - ''The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005)'' - page 126</ref>
 
;H5N1
{{main|H5N1}}
:[[H5N1]] is the world's major [[influenza pandemic]] threat.
 
;H7N7
{{main|H7N7}}
:[[H7N7]] has unusual zoonotic potential. In [[2003]] in [[Netherlands]] 89 people were confirmed to have H7N7 influenza virus infection following an outbreak in poultry on several farms. One death was recorded.
 
;H1N2
{{main|H1N2}}
:[[H1N2]] is currently endemic in both human and pig populations. The new [[H1N2]] strain appears to have resulted from the reassortment of the genes of the currently circulating influenza [[H1N1]] and [[H3N2]] subtypes. The [[hemagglutinin]] protein of the [[H1N2]] virus is similar to that of the currently circulating [[H1N1]] viruses and the [[neuraminidase]] protein is similar to that of the current [[H3N2]] viruses.
 
;H9N2
{{main|H9N2}}
:Low pathogenic avian influenza A ([[H9N2]]) infection was confirmed in [[1999]], in [[China]] and [[Hong Kong]] in two children, and in [[2003]] in [[Hong Kong]] in one child. All three fully recovered. <ref>[http://www.cdc.gov/flu/avian/gen-info/avian-flu-humans.htm CDC] ''Avian Influenza Infection in Humans''</ref>
 
;H7N2
{{main|H7N2}}
:One person in [[New York]] in [[2003]] and one person in [[Virginia]] in [[2002]] were found to have serologic evidence of infection with [[H7N2]]. Both fully recovered. <ref>[http://www.cdc.gov/flu/avian/gen-info/avian-flu-humans.htm CDC] ''Avian Influenza Infection in Humans''</ref>
 
;H7N3
{{main|H7N3}}
:In [[North America]], the presence of avian influenza strain [[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 with avian influenza have been confirmed in that region. "Symptoms included [[conjunctivitis]] and mild [[influenza]]-like illness." <ref>[http://www.cdc.gov/ncidod/EID/vol10no12/04-0961.htm CDC detailed analysis] ''Human Illness from Avian Influenza H7N3, British Columbia''</ref> Both fully recovered.
 
;H10N7
{{main|H10N7}}
:In [[2004]] in [[Egypt]] [[H10N7]] is reported for the first time in humans. It caused illness in two infants in Egypt. One child’s father is a [[poultry]] merchant. <ref>[http://www3.niaid.nih.gov/news/focuson/flu/illustrations/timeline/timeline.htm niaid.nih.gov] Timeline of Human Flu Pandemics</ref>
 
==Variants and subtypes==
{{Taxobox
| name = [[Orthomyxoviridae]]
| image = Influenza A - late passage.jpg
| image_width = 175px
| image_description = Source: Dr. Erskine Palmer, [[Centers for Disease Control and Prevention|CDC]]
| image_caption = [[Electron micrograph]] of Influenza A viruses
| virus_group = v
| familia  = '''''Orthomyxoviridae'''''
| subdivision_ranks = Genera
| subdivision = ''[[Influenzavirus A]]''<br>
''[[Influenzavirus B]]''<br>
''[[Influenzavirus C]]''<br>
''[[Isavirus]]''<br>
''[[Thogotovirus]]
}}
Variants are identified and named according to the isolate that they are like and thus are presumed to share lineage (example [[Fujian flu]] virus like); according to their typical host (example [[Human flu]] virus); according to their subtype (example [[H3N2]]); and according to their deadliness (example LP). So a [[flu]] from a virus similar to the  isolate A/Fujian/411/2002(H3N2) is called Fujian flu, human flu, and H3N2 flu.
 
Variants are sometimes named according to the species (host) the strain is endemic in or adapted to. The main variants named using this convention are:
* [[Avian influenza|Bird flu]]
* [[Human flu|Human Flu]]
* [[Swine flu|Swine Flu]]
* [[Horse flu|Horse Flu]]
* [[Dog flu|Dog Flu]]
 
Avian variants have also sometimes been named according to their deadliness in poultry, especially chickens:
* Low Pathogenic Avian Influenza (LPAI)
* Highly Pathogenic Avian Influenza (HPAI), also called: deadly flu or death flu
 
The Influenza A virus subtypes are labeled according to an H number (for [[hemagglutinin]]) and an N number (for [[neuraminidase]]). Each subtype virus has [[mutate]]d into a variety of strains with differing [[pathogenic]] profiles; some pathogenic to one species but not others, some pathogenic to multiple species. Most known strains are extinct strains. For example, the annual flu subtype [[H3N2]] no longer contains the strain that caused the [[Hong Kong Flu]].
 
Influenza A [[virus]]es are negative sense, single-stranded, segmented [[RNA virus]]es. "There are 16 different HA [[antigen]]s (H1 to H16) and nine different NA [[antigen]]s (N1 to N9) for influenza A. Until recently, 15 HA types had been recognized, but a new type (H16) was isolated from [[black-headed gull]]s caught in [[Sweden]] and the [[Netherlands]] in [[1999]] and reported in the literature in [[2005]]." <ref>[http://id_center.apic.org/cidrap/content/influenza/panflu/biofacts/panflu.html CIDRAP - Center for Infectious Disease Research And Policy] Pandemic Influenza Overview</ref>
 
==Genetics==
"The physical structure of all influenza A viruses is similar. The virions or virus particles are enveloped and can be either spherical or filamentous in form. In clinical isolates that have undergone limited passages in eggs or tissue culture, there are more filamentous than spherical particles, whereas passaged laboratory strains consist mainly of spherical virions."<ref> [http://www.clinicalservicesjournal.com/print.asp?id=872 Clinical Services Journal] article ''Avian influenza issues analysed'' published March 2006</ref>
 
The Influenza A virus genome is contained on eight single (non-paired) RNA strands that code for eleven proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2). The segmented nature of the genome allows for the exchange of entire genes between different viral [[strain (biology)|strains]] during cellular cohabitation. The  eight RNA segments are:
*HA encodes [[hemagglutinin]] (about 500 molecules of [[hemagglutinin]] are needed to make one [[virion]]) "The extent of infection into host organism is determined by HA. Influenza viruses bud from the apical surface of polarized epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs and are therefore usually pneumotropic. The reason is that HA is cleaved by tryptase clara which is restricted to lungs. However HAs of H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and subtilisin-type enzymes, allowing the virus to grow in other organs than lungs." <ref>[http://www.expasy.org/uniprot/P09345 UniProtKB/Swiss-Prot entry P09345] Complete sequence of a cDNA clone of the hemagglutinin gene of influenza A/Chicken/Scotland/59 (H5N1) virus: comparison with contemporary North American and European strains.</ref>
*NA encodes [[neuraminidase]] (about 100 molecules of [[neuraminidase]] are needed to make one [[virion]]).
*NP encodes [[nucleoprotein]].
*M encodes two [[matrix protein]]s (the [[M1 protein|M1]] and the [[M2 protein|M2]]) by using different [[reading frame]]s from the same RNA segment (about 3000  matrix protein molecules are needed to make one [[virion]]).
*NS encodes two distinct non-structural proteins (NS1 and NEP) by using different reading frames from the same RNA segment.
*PA encodes an [[RNA polymerase]].
*PB1 encodes an [[RNA polymerase]] and PB1-F2 protein (induces [[apoptosis]]) by using different reading frames from the same RNA segment.
*PB2 encodes an [[RNA polymerase]].
 
The genome segments have common terminal sequences, and the ends of the RNA strands are partially [[complementarity (molecular biology)|complementary]], allowing them to bond to each other by [[hydrogen bond]]s. After transcription from negative-sense to [[positive-sense RNA]] the +RNA strands get the cellular [[5' cap]] added by cap snatching, which involves the viral protein NS1 binding to the cellular pre-mRNAs. The cap is then cleaved from the cellular pre-mRNA using a second viral protein, PB2. The short [[oligo]] cap is then added to the influenza +RNA strands, allowing its processing as [[messenger RNA]] by [[ribosome]]s. The +RNA strands also serve for synthesis of -RNA strands for new virions.
 
The [[RNA]] synthesis and its assembly with the nucleoprotein takes place in the [[cell nucleus]], the synthesis of proteins takes place in the [[cytoplasm]]. The assembled virion cores leave the nucleus and migrate towards the [[cell membrane]], with patches of viral [[transmembrane protein]]s (hemagglutinin, neuraminidase and M2 proteins) and an underlying layer of the M1 protein, and [[budding|bud]] through these patches, releasing finished enveloped [[virus]]es into the [[extracellular fluid]].
 
 
 
;Swine flu
{{main|Swine Flu}}
:[[Swine flu]] (or "pig influenza") refers to a subset of [[Orthomyxoviridae]] that create [[influenza]] in [[pigs]] and are [[endemic (epidemiology)|endemic]] in pigs. The species of [[Orthomyxoviridae]] that can cause flu in pigs are Influenza A virus and [[Influenzavirus C|Influenza C virus]] but not all genotypes of these two species infect pigs. The known subtypes of Influenza A virus that create [[influenza]] in [[pigs]] and are [[endemic (epidemiology)|endemic]] in pigs are [[H1N1]], [[H1N2]], [[H3N1]] and [[H3N2]].
 
;Horse flu
{{main|Horse flu}}
:[[Horse flu]] (or "Equine influenza") refers to varieties of Influenza A virus that affect horses. Horse 'flu viruses were only isolated in 1956. There are two main types of virus called equine-1 ([[H7N7]]) which commonly affects horse heart muscle and equine-2 ([[H3N8]]) which is usually more severe.
 
;Dog flu
{{main|Dog flu}}
:[[Dog flu]] (or "canine influenza") refers to varieties of Influenza A virus that affect dogs. The equine influenza virus [[H3N8]] was found to infect and kill greyhound race dogs that had died from a respiratory illness at a Florida racetrack in [[January 2004]].
 
;H3N8
{{main|H3N8}}
:[[H3N8]] is now endemic in birds, horses and dogs.
 
==See also==
 
* [[Animal virology]]
* [[ACAM-FLU-A]]
 
==References==
{{reflist|2}}
 
[[Category:H5N1]]
[[Category:Zoonoses]]
[[Category:Orthomyxoviridae]]


==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:Primary care]]
[[Category:Orthomyxoviridae]]
{{WH}}
{{WS}}

Latest revision as of 22:24, 29 July 2020

Influenza Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Influenza from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

Other Diagnostic Studies

Treatment

Medical Therapy

Primary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Influenza causes On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Influenza causes

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Influenza causes

CDC on Influenza causes

Influenza causes in the news

Blogs on Influenza causes

Directions to Hospitals Treating Influenza

Risk calculators and risk factors for Influenza causes

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".

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Influenza_causes&oldid=1639884"