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]
Variants and subtypes
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 Electron micrograph of Influenza A viruses
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| style="background:#Template:Taxobox colour;" | Virus classification | ||||
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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." [4]
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." [5].
The annually updated trivalent influenza vaccine consists of hemagglutinin (HA) surface glycoprotein components from influenza H3N2, H1N1, and B influenza viruses. [6]
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." [7]
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."[8]
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." [9]
- 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 .
- ↑ 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.