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Human influenza is a term used to refer to influenza cases caused by Orthomyxoviridae that are endemic to human populations (as opposed to infection relying upon zoonosis). It is an arbitrary categorization scheme, and is not associated with phylogenetics-based taxonomy. Human influenza-causing viruses can belong to any of three major influenza-causing Orthomyxoviruses — Influenza A virus, Influenza B virus and Influenza C virus.
Most human influenza is a non-pandemic influenza that is slightly different from the main human flus that existed in the previous year's flu season period. It causes yearly influenza epidemics that are generally not deadly except to the very old or very young.
Genetic factors distinguishing between "human influenza 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.
"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 influenza viruses." "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."
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 depends to a large part on the state of the infected person's immune system and whether the victim has been previously exposed to the strain and is therefore partially immune.
All of these symptoms are characteristic of numerous infectious agents, so many that most diagnoses of human influenza technically are diagnoses of influenza-like illness (ILI) and most cases of ILI are not due to influenza.
||The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. (December 2010)|
The annual 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."
According to the World Health Organization: "Every winter, tens of millions of people get the flu. Most are only ill and out of work for a week, yet the elderly are at a higher risk of death from the illness. We know the worldwide death toll exceeds a few hundred thousand people a year, but even in developed countries the numbers are uncertain, because medical authorities don't usually verify who actually died of influenza and who died of a flu-like illness."
The Influenza A virus subtypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:
- H1N1 caused "Spanish Influenza" and a reassortment caused the 2009 swine influenza outbreak
- H2N2 caused "Asian Influenza"
- H3N2 caused "Hong Kong Influenza"
- H5N1 "The Bird Influenza" was the world's major influenza pandemic threat until the Swine Flu Pandemic of 2009.
- H7N7 has unusual zoonotic potential
- H1N2 is currently endemic in humans and pigs
- H9N2, H7N2, H7N3, H10N7.
- 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. 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." 
- The Asian Flu was a pandemic outbreak of H2N2 avian influenza that originated in China in 1957, spread worldwide that same year during which an influenza vaccine was developed, lasted until 1958 and caused between one and four million deaths.
- 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. "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." 
- 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.
- "[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." 
- H5N1 was the world's major influenza pandemic threat until the swine flu epidemic of 2009—a new strain of H1N1.
- 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 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.
- 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.
- 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.
- 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."  Both fully recovered.
- In 2004 in Egypt H10N7 was reported for the first time in humans. It caused illness in two infants in Egypt. One child’s father is a poultry merchant.
Influenza B viruses are only known to infect humans and seals, giving them influenza. This limited host range is apparently responsible for the lack of Influenzavirus B caused influenza pandemics in contrast with those caused by the morphologically similar Influenzavirus A as both mutate by both genetic drift and reassortment.
Flu due to the type C species is rare compared to types A or B, but can be severe and cause local epidemics. Yearly vaccines do not vaccinate against type C.
Sources and notes
- CDC Key Facts About Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) Virus
- 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
- 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."
- Peter M. Sandman and Jody Lanard "Bird Flu: Communicating the Risk" 2005 Perspectives in Health Magazine Vol. 10 issue 2.
- NAP Books National Academies Press Books - The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) - page 7.
- Kolata, Gina (November 8, 2005). "Hazard in Hunt for New Flu: Looking for Bugs in All the Wrong Places". The New York Times.
- 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 Altman, Lawrence K. (January 15, 2006). "This Season's Flu Virus Is Resistant to 2 Standard Drugs". The New York Times.
- 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 detailed analysis Human Illness from Avian Influenza H7N3, British Columbia
- niaid.nih.gov Timeline of Human Flu Pandemics
- Osterhaus AD, Rimmelzwaan GF, Martina BE, Bestebroer TM, Fouchier RA (2000). "Influenza B virus in seals". Science 288 (5468): 1051–3. doi:10.1126/science.288.5468.1051. PMID 10807575.
- Hay AJ, Gregory V, Douglas AR, Lin YP (2001). "The evolution of human influenza viruses". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356 (1416): 1861–70. doi:10.1098/rstb.2001.0999. PMC 1088562. PMID 11779385.
- Matsuzaki Y, Sugawara K, Takashita E, Muraki Y, Hongo S, Katsushima N, Mizuta K, Nishimura H (2004). "Genetic diversity of influenza B virus: the frequent reassortment and cocirculation of the genetically distinct reassortant viruses in a community". J. Med. Virol. 74 (1): 132–40. doi:10.1002/jmv.20156. PMID 15258979.
- Lindstrom SE, Hiromoto Y, Nishimura H, Saito T, Nerome R, Nerome K (1999). "Comparative Analysis of Evolutionary Mechanisms of the Hemagglutinin and Three Internal Protein Genes of Influenza B Virus: Multiple Cocirculating Lineages and Frequent Reassortment of the NP, M, and NS Genes". J. Virol. 73 (5): 4413–26. PMC 104222. PMID 10196339.