Influenza causes
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
Overview
Template:FluTemplate:H5N1 Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Influenzavirus A includes only one species: Influenza A virus which causes influenza in birds and some mammals. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon. Some isolates of influenza A virus cause severe disease both in domestic poultry and, rarely, in humans.[1] Occasionally viruses are transmitted from wild aquatic birds to domestic poultry and this may cause an outbreak or give rise to human influenza pandemics.[2] [3]
Taxonomy
- There are three types of influenza viruses: A, B and C.
- Human influenza A and B viruses cause seasonal epidemics of disease almost every winter in the United States.
- 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.
- 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)
- The host of origin (e.g., swine, equine, chicken, etc. For human-origin viruses, no host of origin designation is given.)
- Geographical origin (e.g., Denver, Taiwan, etc.)
- Strain number (e.g., 15, 7, etc.)
- Year of isolation (e.g., 57, 2009, etc.)
- For influenza A viruses, the hemagglutinin and neuraminidase antigen description in parentheses (e.g., (H1N1), (H5N1)
- 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.
- Genetic factors in distinguishing between "human flu viruses" and "avian influenza viruses" include:
- 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 Glu at position 627, while all human influenza viruses had a lysine.
- 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.
Influenza A
"About 52 key genetic changes distinguish avian influenza strains from those that spread easily among people, according to researchers in Taiwan, who analyzed the genes of more than 400 A type flu viruses."[4] "How many mutations would make an avian virus capable of infecting humans efficiently, or how many mutations would render an influenza virus a pandemic strain, is difficult to predict. We have examined sequences from the 1918 strain, which is the only pandemic influenza virus that could be entirely derived from avian strains. Of the 52 species-associated positions, 16 have residues typical for human strains; the others remained as avian signatures. The result supports the hypothesis that the 1918 pandemic virus is more closely related to the avian influenza A virus than are other human influenza viruses."[5]
Human flu symptoms usually include fever, cough, sore throat, muscle aches, conjunctivitis and, in severe cases, severe breathing problems and pneumonia that may be fatal. The severity of the infection will depend to a large part on the state of the infected person's immune system and if the victim has been exposed to the strain before, and is therefore partially immune.
Highly pathogenic H5N1 avian influenza in a human is far worse, killing 50% of humans that catch it. In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms. [6]
The Influenza A virus subtypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:
- H1N1 caused "Spanish Flu"
- H2N2 caused "Asian Flu"
- H3N2 caused "Hong Kong Flu"
- H5N1 is the world's major influenza pandemic threat
- H7N7 has unusual zoonotic potential
- H1N2 is currently endemic in humans and pigs
- H9N2, H7N2, H7N3, H10N7.
- H1N1
- 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. [7] Controversy arose in October, 2005, after the H1N1 genome was published in the journal, Science. Many fear that this information could be used for bioterrorism.
- "When he compared the 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." [8]
- H2N2
- 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.
- H3N2
- 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. [9] "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." [10]
- 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. [11]
- "[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." [12]
- H5N1
- H5N1 is the world's major influenza pandemic threat.
- 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
- 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
- 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. [13]
- 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. [14]
- 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." [15] Both fully recovered.
- 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. [16]
Variants and subtypes
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 Electron micrograph of Influenza A viruses
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Influenzavirus A |
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 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 mutated 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 viruses are negative sense, single-stranded, segmented RNA viruses. "There are 16 different HA antigens (H1 to H16) and nine different NA antigens (N1 to N9) for influenza A. Until recently, 15 HA types had been recognized, but a new type (H16) was isolated from black-headed gulls caught in Sweden and the Netherlands in 1999 and reported in the literature in 2005." [17]
Annual flu
The annual flu (also called "seasonal flu" or "human flu") in the U.S. "results in approximately 36,000 deaths and more than 200,000 hospitalizations each year. In addition to this human toll, influenza is annually responsible for a total cost of over $10 billion in the U.S." [18].
The annually updated trivalent influenza vaccine consists of hemagglutinin (HA) surface glycoprotein components from influenza H3N2, H1N1, and B influenza viruses. [19]
The dominant strain 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.
"[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." [20]
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."[21]
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 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." [22]
- NA encodes neuraminidase (about 100 molecules of neuraminidase are needed to make one virion).
- NP encodes nucleoprotein.
- M encodes two matrix proteins (the M1 and the M2) by using different reading frames 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 complementary, allowing them to bond to each other by hydrogen bonds. 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 ribosomes. 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 proteins (hemagglutinin, neuraminidase and M2 proteins) and an underlying layer of the M1 protein, and bud through these patches, releasing finished enveloped viruses into the extracellular fluid.
- Swine flu
- Swine flu (or "pig influenza") refers to a subset of Orthomyxoviridae that create influenza in pigs and are endemic in pigs. The species of Orthomyxoviridae that can cause flu in pigs are Influenza A virus and 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 in pigs are H1N1, H1N2, H3N1 and H3N2.
- 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
- 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
- H3N8 is now endemic in birds, horses and dogs.
See also
Further reading
- Official sources
- Avian influenza and Influenza Pandemics from the Centers for Disease Control and Prevention
- Avian influenza FAQ from the World Health Organization
- Avian influenza information from the Food and Agriculture Organization
- U.S. Government's avian influenza information website
- European Centre for Disease Prevention and Control (ECDC) Stockholm, Sweden
- General information
- "The Bird Flu and You" Full-color poster provided by the Center for Technology and National Security Policy at the National Defense University, in collaboration with the National Security Health Policy Center
- Influenza Report 2006 Online book. Research level quality information. Highly recommended.
- Special issue on avian flu from Nature
- Overview of H5N1 from New England Journal of Medicine
- Pandemic Influenza: Domestic Preparedness Efforts Congressional Research Service Report on Pandemic Preparedness.
- A guide to bird flu and its symptoms from BBC Health
- A Variety of Avian Flu Images and Pictures
- Avian flu, bioterror, animals (page in an online book) "Highly pathogenic avian influenza virus is on every top ten list available for potential agricultural bioweapon agents"
- 'The Threat of Bird Flu': HealthPolitics.com
- Is a Global Flu Pandemic Imminent? from Infection Control Today.
- Bird Flu is a Real Pandemic Threat to Humans by Leonard Crane, author of Ninth Day of Creation.
- Links to Bird Flu pictures (Hardin MD/Univ of Iowa)
- Flu Wiki
- Influenza Virology: Current Topics ISBN 978-1-904455-06-6
- Animal Viruses: Molecular Biology ISBN 978-1-904455-22-6
- News
- Current status (Google news of avian OR bird flu OR influenza)
- Flu Breaking News Avian flu, common symptom, influenza vaccine and flu shot and latest news
- Global Pandemic News : 24×7 online news feeds on the threat of Bird Flu and a Global Pandemic
References
- ↑ WHO Avian influenza (" bird flu") - Fact sheet
- ↑ Klenk; et al. (2008). "Avian Influenza: Molecular Mechanisms of Pathogenesis and Host Range". Animal Viruses: Molecular Biology. Caister Academic Press. ISBN 978-1-904455-22-6.
- ↑ Kawaoka Y (editor). (2006). Influenza Virology: Current Topics. Caister Academic Press. ISBN 978-1-904455-06-6 .
- ↑ Bloomberg News article Scientists Move Closer to Understanding Flu Virus Evolution published August 28, 2006
- ↑ CDC Emerging Infectious Diseases Journal Volume 12, Number 9 – September 2006 - Genomic Signatures of Human versus Avian Influenza A Viruses article by Chen G-W, Chang S-C, Mok C-K, Lo Y-L, Kung Y-N, Huang J-H, et al. posted August 23, 2006
- ↑ New England Journal of Medicine Volume 352:686-691 - February 17, 2005 - Number 7 - Fatal Avian Influenza A (H5N1) in a Child Presenting with Diarrhea Followed by Coma
- ↑ NAP Books National Academies Press Books - The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) - page 7.
- ↑ New York Times Published: November 8, 2005 - Hazard in Hunt for New Flu: Looking for Bugs in All the Wrong Places
- ↑ Detailed chart of its evolution here at PDF called Ecology and Evolution of the Flu
- ↑ 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."
- ↑ Reason New York Times This Season's Flu Virus Is Resistant to 2 Standard Drugs By Altman Published: January 15, 2006
- ↑ NAP Books National Academies Press Books - The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) - page 126
- ↑ CDC Avian Influenza Infection in Humans
- ↑ CDC Avian Influenza Infection in Humans
- ↑ CDC detailed analysis Human Illness from Avian Influenza H7N3, British Columbia
- ↑ niaid.nih.gov Timeline of Human Flu Pandemics
- ↑ CIDRAP - Center for Infectious Disease Research And Policy Pandemic Influenza Overview
- ↑ whitehouse.gov National Strategy for Pandemic Influenza - Introduction - "Although remarkable advances have been made in science and medicine during the past century, we are constantly reminded that we live in a universe of microbes - viruses, bacteria, protozoa and fungi that are forever changing and adapting themselves to the human host and the defenses that humans create. Influenza viruses are notable for their resilience and adaptability. While science has been able to develop highly effective vaccines and treatments for many infectious diseases that threaten public health, acquiring these tools is an ongoing challenge with the influenza virus. Changes in the genetic makeup of the virus require us to develop new vaccines on an annual basis and forecast which strains are likely to predominate. As a result, and despite annual vaccinations, the U.S. faces a burden of influenza that results in approximately 36,000 deaths and more than 200,000 hospitalizations each year. In addition to this human toll, influenza is annually responsible for a total cost of over $10 billion in the U.S. A pandemic, or worldwide outbreak of a new influenza virus, could dwarf this impact by overwhelming our health and medical capabilities, potentially resulting in hundreds of thousands of deaths, millions of hospitalizations, and hundreds of billions of dollars in direct and indirect costs. This Strategy will guide our preparedness and response activities to mitigate that impact."
- ↑ CDC Centers for Disease Control and Prevention - Research Article - Influenza A (H3N2) Outbreak, Nepal - "The 2003–2004 influenza season was severe in terms of its impact on illness because of widespread circulation of antigenically distinct influenza A (H3N2) Fujian-like viruses. These viruses first appeared late during the 2002–2003 influenza season and continued to persist as the dominant circulating strain throughout the subsequent 2003–2004 influenza season, replacing the A/Panama/2007/99-like H3N2 viruses (1). Of the 172 H3N2 viruses genetically characterized by the Department of Defense in 2003–2004, only 1 isolate (from Thailand) belonged to the A/Panama-like lineage. In February 2003, the World Health Organization (WHO) changed the H3N2 component for the 2004–2005 influenza vaccine to afford protection against the widespread emergence of Fujian-like viruses (2). The annually updated trivalent vaccine consists of hemagglutinin (HA) surface glycoprotein components from influenza H3N2, H1N1, and B viruses."
- ↑ NAP Books National Academies Press - Books - "The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005)" - page 126 - "H5N1 virus is now endemic in poultry in Asia (Table 2-1) and has gained an entrenched ecological niche from which to present a long-term pandemic threat to humans. At present, these viruses are poorly transmitted from poultry to humans, and there is no conclusive evidence of human-to-human transmission. However, continued, extensive exposure of the human population to H5N1 viruses increases the likelihood that the viruses will acquire the necessary characteristics for efficient human-to-human transmission through genetic mutation or reassortment with a prevailing human influenza A virus. Furthermore, contemporary human H3N2 influenza viruses are now endemic in pigs in southern China (Peiris et al., 2001) and can reassort with avian H5N1 viruses in this 'intermediate host.' Therefore, it is imperative that outbreaks of H5N1 disease in poultry in Asia are rapidly and sustainably controlled. The seasonality of the disease in poultry, together with the control measures already implemented, are likely to reduce temporarily the frequency of H5N1 influenza outbreaks and the probability of human infection."
- ↑ Clinical Services Journal article Avian influenza issues analysed published March 2006
- ↑ 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.