RhinovirusFrom Wikipedia, the free encyclopedia "Human rhinovirus"

Molecular surface of a Human rhinovirus, showing protein spikes

Virus classification Group: Group IV ((+)ssRNA) Order: Picornavirales Family: Picornaviridae Genus: Enterovirus Type species Human enterovirus C Species Human rhinovirus A Human rhinovirus B Human rhinovirus C Human rhinoviruses (from the Greek , (gen.) "nose") are the most common viral infective agents in humans and are the predominant cause of the common cold. Rhinovirus infection proliferates in temperatures between 3335 C (9195 F), and this may be why it occurs primarily in the nose. Rhinovirus is a species in the genus Enterovirus of the Picornaviridae family of viruses. There are 99 recognized types of Human rhinoviruses that differ according to their surface proteins. They are lytic in nature and are among the smallest viruses, with diameters of about only 30 nanometers. Other viruses such as smallpox and vaccinia are around 10 times larger at about 300 nanometers.

Contents[hide]

1 Transmission and epidemiology

2 Pathogenesis 3 Taxonomy 4 Structure 5 Novel antiviral drugs 6 Vaccine 7 References 8 External links

[edit] Transmission and epidemiologyMain article: Common cold There are two modes of transmission: via aerosols of respiratory droplets and from contaminated surfaces, including direct person-to-person contact. Human rhinoviruses occur worldwide and are the primary cause of common colds. Symptoms include sore throat, runny nose, nasal congestion, sneezing and cough; sometimes accompanied by muscle aches, fatigue, malaise, headache, muscle weakness, or loss of appetite. Fever and extreme exhaustion are more usual in influenza. Children may have six to twelve colds a year. In the United States, the incidence of colds is higher in the autumn and winter, with most infections occurring between September to April. The seasonality may be due to the start of the school year, or due to people spending more time indoors (thus in closer proximity with each other), increasing the chance of transmission of the virus.

[edit] PathogenesisThe primary route of entry for Human rhinoviruses is the upper respiratory tract. Afterward, the virus binds to ICAM-1 (Inter-Cellular Adhesion Molecule 1) also known as CD54 (Cluster of Differentiation 54) receptors on respiratory epithelial cells. As the virus replicates and spreads, infected cells release distress signals known as chemokines and cytokines (which in turn activate inflammatory mediators). Infection occurs rapidly, with the virus adhering to surface receptors within 15 minutes of entering the respiratory tract. Just over 50% of symptomatic individuals will experience symptoms within 2 days of infection. Only about 5% of cases will have an incubation period of less than 20 hours, and, on the other end, it is expected that 5% of cases would have an incubation period of greater than four and a half days.[1] Human rhinoviruses preferentially grow at 32C (89F) as opposed to 37C (98F), hence infect the upper respiratory tract.

[edit] Taxonomy

Rhinovirus was formerly a genus from the family Picornaviridae. The 39th Executive Committee (EC39) of the International Committee on Taxonomy of Viruses (ICTV) met in Canada during June 2007 with new taxonomic proposals. In April 2008, the International Committee on Taxonomy of Viruses voted and ratified the following changes:

2005.264V.04 To remove the following species from the existing genus Rhinovirus in the family Picornaviridae: o Human rhinovirus A o Human rhinovirus B 2005.265V.04 To assign the following species to the genus Enterovirus in the family Picornaviridae: o Human rhinovirus A o Human rhinovirus B 2005.266V.04 To remove the existing genus Rhinovirus from the family Picornaviridae. Note: The genus Rhinovirus hereby disappears.

In July 2009, the ICTV voted and ratified a proposal to add a third species, Human rhinovirus C to the genus Enterovirus.

2008.084V.A.HRV-C-Sp 2008.084V To create a new species named Human rhinovirus C in the genus Enterovirus, family Picornaviridae.

There have been a total of 215 taxonomic proposals, which have been approved and ratified since the 8th ICTV Report of 2005. Rhinovirus C, unlike the A and B species, may be able to cause severe infections.[2]

[edit] StructureRhinoviruses have single-stranded positive sense RNA genomes of between 7.2 and 8.5 kb in length. At the 5' end of the genome is a virus-encoded protein, and like mammalian mRNA, there is a 3' poly-A tail. Structural proteins are encoded in the 5' region of the genome and non structural at the 3' end. This is the same for all picornaviruses. The viral particles themselves are not enveloped and are icosahedral in structure. The viral proteins are transcribed as a single, long polypeptide, which is cleaved into the structural and nonstructural viral proteins.[3] Human rhinoviruses are composed of a capsid, that contains four viral proteins VP1, VP2, VP3 and VP4.[4][5] VP1, VP2, and VP3 form the major part of the protein capsid. The much smaller VP4 protein has a more extended structure, and lies at interface between the capsid and the RNA genome. There are 60 copies of each of these proteins assembled as an icosahedron. Antibodies are a major defense against infection with the epitopes lying on the exterior regions of VP1-VP3.

[edit] Novel antiviral drugsInterferon-alpha used intranasally was shown to be effective against Human rhinovirus infections. However, volunteers treated with this drug experienced some side effects, such as nasal bleeding, and began developing resistance to the drug. Subsequently, research into the treatment was abandoned. Pleconaril is an orally bioavailable antiviral drug being developed for the treatment of infections caused by picornaviruses.[6] This drug acts by binding to a hydrophobic pocket in VP1, and stabilizes the protein capsid to such an extent that the virus cannot release its RNA genome into the target cell. When tested in volunteers, during the clinical trials, this drug caused a significant decrease in mucus secretions and illness-associated symptoms. Pleconaril is not currently available for treatment of Human rhinoviral infections, as its efficacy in treating these infections is under further evaluation.[7] There are potentially other substances such as Iota-Carrageenan that may lead to the creation of drugs to combat the Human rhinovirus.[8] In Asthma: Human rhinoviruses have been recently associated with the majority of asthma exacerbations for which current therapy is inadequate. Intercellular adhesion molecule 1 (ICAM1) has a central role in airway inflammation in asthma, and it is the receptor for 90% of Human rhinoviruses. Human rhinovirus infection of airway epithelium induces ICAM-1. Desloratadine and loratadine are compounds belonging to the new class of H1-receptor blockers. Antiinflammatory properties of antihistamines have been recently documented, although the underlying molecular mechanisms are not completely defined. These effects are unlikely to be mediated by H1-receptor antagonism and suggest a novel mechanism of action that may be important for the therapeutic control of virus-induced asthma exacerbations.

[edit] VaccineThere are no vaccines against these viruses as there is little-to-no cross-protection between serotypes. At least 99 serotypes of Human rhinoviruses affecting humans have been sequenced.[9] [10] However, recent study of the VP4 protein has shown it to be highly conserved amongst many serotypes of Human rhinovirus,[11] opening up the potential for a future pan-serotype Human rhinovirus vaccine.

CoronavirusFrom Wikipedia, the free encyclopedia Coronavirus

Virus classification Group: Group IV ((+)ssRNA) Order: Nidovirales Family: Coronaviridae Subfamily: Coronavirinae Genus Alphacoronavirus Betacoronavirus Gammacoronavirus Coronaviruses are species in the genera of virus belonging to the subfamily Coronavirinae in the family Coronaviridae.[1] Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome and a helical symmetry. The genomic size of coronaviruses ranges from approximately 16 to 31 kilobases, extraordinarily large for an RNA virus. The name "coronavirus" is derived from the Greek , meaning crown, as the virus envelope appears under electron microscopy (E.M.) to be crowned by a characteristic ring of small bulbous structures. This morphology is actually formed by the viral spike (S) peplomers, which are proteins that populate the surface of the virus and determine host tropism. Coronaviruses are grouped in the order Nidovirales, named for the Latin nidus, meaning nest, as all viruses in this order produce a 3' co-terminal nested set of subgenomic mRNA's during infection. Proteins that contribute to the overall structure of all coronaviruses are the spike (S), envelope (E), membrane (M) and nucleocapsid (N). In the specific case of SARS (see below), a defined receptor-binding domain on S mediates the attachment of the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2).[2] Members of the group 2 coronaviruses also have a shorter spike-like protein called hemagglutinin esterase (HE) encoded in their genome, but for some reason this protein is not always brought to expression (produced) in the cell.[3]

Contents[hide]

1 Diseases of coronavirus 2 Replication 3 Severe acute respiratory syndrome

4 Recent discoveries of novel human coronaviruses 5 Species 6 References 7 External links

[edit] Diseases of coronavirusCoronaviruses primarily infect the upper respiratory and gastrointestinal tract of mammals and birds. Four to five different currently known strains of coronaviruses infect humans. The most publicized human coronavirus, SARS-CoV which causes SARS, has a unique pathogenesis because it causes both upper and lower respiratory tract infections and can also cause gastroenteritis. Coronaviruses are believed to cause a significant percentage of all common colds in human adults. Coronaviruses cause colds in humans primarily in the winter and early spring seasons. The significance and economic impact of coronaviruses as causative agents of the common cold are hard to assess because, unlike rhinoviruses (another common cold virus), human coronaviruses are difficult to grow in the laboratory. Coronaviruses also cause a range of diseases in farm animals and domesticated pets, some of which can be serious and are a threat to the farming industry. Economically significant coronaviruses of farm animals include porcine coronavirus (transmissible gastroenteritis coronavirus, TGE) and bovine coronavirus, which both result in diarrhea in young animals. Feline Coronavirus: 2 forms, Feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneous mutation of this virus can result in feline infectious peritonitis (FIP), a disease associated with high mortality. There are two types of canine coronavirus (CCoV), one that causes mild gastrointestinal disease and one that has been found to cause respiratory disease. Mouse hepatitis virus (MHV) is a coronavirus that causes an epidemic murine illness with high mortality, especially among colonies of laboratory mice. Prior to the discovery of SARS-CoV, MHV had been the best-studied coronavirus both in vivo and in vitro as well as at the molecular level. Some strains of MHV cause a progressive demyelinating encephalitis in mice which has been used as a murine model for multiple sclerosis. Significant research efforts have been focused on elucidating the viral pathogenesis of these animal coronaviruses, especially by virologists interested in veterinary and zoonotic diseases.

[edit] Replication

The infection cycle of coronavirus Replication of Coronavirus begins with entry to the cell takes place in the cytoplasm in a membrane-protected microenvironment, upon entry to the cell the virus particle is uncoated and the RNA genome is deposited into the cytoplasm. The Coronavirus genome has a 5 methylated cap and a 3polyadenylated-A tail to make it look as much like the host RNA as possible. This also allows the RNA to attach to ribosomes for translation. Coronaviruses also have a protein known as a replicase encoded in its genome which allows the RNA viral genome to be transcribed into new RNA copies using the host cells machinery. The replicase is the first protein to be made as once the gene encoding the replicase is translated the translation is stopped by a stop codon. This is known as a nested transcript, where the transcript only encodes one gene- it is monocistronic. The RNA genome is replicated and a long polyprotein is formed, where all of the proteins are attached. Coronaviruses have a non-structural protein called a protease which is able to separate the proteins in the chain. This is a form of genetic economy for the virus allowing it to encode the most amounts of genes in a small amount of nucleotides. Coronavirus transcription involves a discontinuous RNA synthesis (template switch) during the extension of a negative copy of the subgenomic mRNAs. Basepairing during transcription is a requirement. Coronavirus N protein is required for coronavirus RNA synthesis, and has RNA chaperone activity that may be involved in template switch. Both viral and cellular proteins are required for replication and transcription. Coronaviruses initiate translation by cap-dependent and cap-independent mechanisms. Cell macromolecular synthesis may be controlled after Coronavirus infection by locating some virus proteins in the host cell nucleus. Infection by different coronaviruses cause in the host alteration in the transcription and translation patterns, in the cell cycle, the cytoskeleton, apoptosis and coagulation pathways, inflammation, and immune and stress responses.[4]

[edit] Severe acute respiratory syndromeMain article: Severe acute respiratory syndrome

In 2003, following the outbreak of Severe acute respiratory syndrome (SARS) which had begun the prior year in Asia, and secondary cases elsewhere in the world, the World Health Organization issued a press release stating that a novel coronavirus identified by a number of laboratories was the causative agent for SARS. The virus was officially named the SARS coronavirus (SARS-CoV). The SARS epidemic resulted in over 8000 infections, about 10% of which resulted in death.[2] Xray crystallography studies performed at the Advanced Light Source of Lawrence Berkeley National Laboratory have begun to give hope of a vaccine against the disease "since [the spike protein] appears to be recognized by the immune system of the host."[5]

[edit] Recent discoveries of novel human coronavirusesFollowing the high-profile publicity of SARS outbreaks, there has been a renewed interest in coronaviruses in the field of virology. For many years, scientists knew only about the existence of two human coronaviruses (HCoV-229E and HCoV-OC43). The discovery of SARS-CoV added another human coronavirus to the list. By the end of 2004, three independent research labs reported the discovery of a fourth human coronavirus. It has been named NL63, NL or the New Haven coronavirus by the different research groups.[6] The naming of this fourth coronavirus is still a controversial issue, because the three labs are still battling over who actually discovered the virus first and hence earns the right to name the virus. Early in 2005, a research team at the University of Hong Kong reported finding a fifth human coronavirus in two pneumonia patients, and subsequently named it HKU1.

[edit] Species

Genus: Alphacoronavirus; type species: Alphacoronavirus 1 o Species: Alphacoronavirus 1, Human coronavirus 229E, Human coronavirus NL63, Miniopterus Bat coronavirus 1, Miniopterus Bat coronavirus HKU8, Porcine epidemic diarrhea virus, Rhinolophus Bat coronavirus HKU2, Scotophilus Bat coronavirus 512 Genus Betacoronavirus; type species: Murine coronavirus o Species: Betacoronavirus 1, Human coronavirus HKU1, Murine coronavirus, Pipistrellus Bat coronavirus HKU5, Rousettus Bat coronavirus HKU9, Severe acute respiratory syndrome-related coronavirus, Tylonycteris Bat coronavirus HKU4 Genus Gammacoronavirus; type species: Avian coronavirus o Species: Avian coronavirus, Beluga whale coronavirus SW1

In April 2008, the following proposals were ratified by the ICTV:[7]

2005.260V.04 To create the following species in the genus Coronavirus in the family Coronaviridae, named Goose coronavirus, Pigeon coronavirus, Duck coronavirus. 2006.009V.04 To create a species in the genus Coronavirus in the family Coronaviridae, named Human coronavirus NL63.

2006.010V.04 To create a species in the genus Coronavirus in the family Coronaviridae, named Human coronavirus HKU1. 2006.011V.04 To create a species in the genus Coronavirus in the family Coronaviridae, named Equine coronavirus.

In July 2009, the following proposals were ratified by the ICTV:[8]

2008.085-122V.A.v3.Coronaviridae 2008.085V Create a new subfamily in the family Coronaviridae, order Nidovirales 2008.086V Name the new subfamily Coronavirinae 2008.087V Create a new genus in the proposed subfamily Coronavirinae 2008.088V Name the new genus Alphacoronavirus 2008.089V Assign three existing species (Human coronavirus 229E, Human coronavirus NL63, Porcine epidemic diarrhea virus) and five new species proposed in 2008.091095V.01 to the proposed new genus Alphacoronavirus 2008.090V Designate proposed species Alphacoronavirus 1 as type species of the genus Alphacoronavirus 2008.091V Create new species named Alphacoronavirus 1 in the new genus 2008.092V Create new species named Rhinolophus bat coronavirus HKU2 in the new genus 2008.093V Create new species named Scotophilus bat coronavirus 512 in the new genus 2008.094V Create new species named Miniopterus bat coronavirus 1 in the new genus 2008.095V Create new species named Miniopterus bat coronavirus HKU8 in the new genus 2008.096V Create a new genus in the proposed subfamily Coronavirinae 2008.097V Name the new genus Betacoronavirus 2008.098V Assign the existing species Human coronavirus HKU1 and six new species proposed in 2008.100-105V.01 to the proposed genus Betacoronavirus 2008.099V Designate proposed species Murine coronavirus as type species of the genus Betacoronavirus 2008.108V Assign the two species proposed in 2008.110,111V.01 to the new genus 2008.109V Designate proposed species Avian coronavirus as type species of the new genus 2008.110V Create species named Avian coronavirus in the new genus 2008.111V Create species named Beluga whale coronavirus SW1 in the new genus 2008.112V Create a new subfamily in the family Coronaviridae, order Nidovirales 2008.113V Name the new subfamily Torovirinae 2008.114V Create a new genus in the subfamily Torovirinae 2008.115V Name the new genus Bafinivirus 2008.116V Assign the species White breamVirus (proposed in 2008.118V.01) to the new genus 2008.117V Designate species White bream virus as type species in the new genus 2008.118V Create species named White bream virus in the new genus 2008.119V Remove the genus Torovirus from the family Coronaviridae 2008.120V Reassign the genus Torovirus to the subfamily Torovirinae

2008.121V.U Remove (abolish) 18 species (Human enteric coronavirus, Human coronavirus OC43, Bovine coronavirus, Porcine hemagglutinating encephalomyelitis virus, Equine coronavirus, Murine hepatitis virus, Puffinosis coronavirus, Rat coronavirus, Transmissible gastroenteritis virus, Canine coronavirus, Feline coronavirus, Infectious bronchitis virus, Duck coronavirus, Goose coronavirus, Pheasant coronavirus, Pigeon coronavirus, Turkey coronavirus, Severe acute respiratory syndrome coronavirus) from the genus Coronavirus 2008.122V.U Reassign species Human coronavirus 229E, Human coronavirus NL63 and Porcine epidemic diarrhea virus to the new genus Alphacoronavirus and Human coronavirus HKU1 to the new genus Betacoronavirus

OrthomyxoviridaeFrom Wikipedia, the free encyclopedia (Redirected from Influenza virus) Orthomyxoviridae Virus classification Group: Group V ((-)ssRNA) Order: Unassigned Family: Orthomyxoviridae Genera

Influenzavirus A Influenzavirus B Influenzavirus C Isavirus Thogotovirus

Influenza (Flu)

Types

Avian (A/H5N1 subtype) Canine Equine Swine (A/H1N1 subtype)

Vaccines

2009 pandemic (Pandemrix) ACAM-FLU-A Fluzone Influvac Live attenuated (FluMist) Optaflu

Treatment

Amantadine Arbidol Laninamivir Oseltamivir Peramivir Rimantadine Vitamin D Zanamivir

Pandemics

2009 Swine 19681969 Hong Kong 1918

Outbreaks

2008 West Bengal 2007 Bernard Matthews H5N1

2007 Australian equine 2006 H5N1 India 1976 swine flu

See also

Flu season Influenza evolution Influenza research Influenza-like illness

vde

The Orthomyxoviridae (orthos, Greek for "straight"; myxa, Greek for "mucus")[1] are a family of RNA viruses that includes five genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus and Thogotovirus. A sixth has recently been described.[2] The first three genera contain viruses that cause influenza in vertebrates, including birds (see also avian influenza), humans, and other mammals. Isaviruses infect salmon; thogotoviruses infect vertebrates and invertebrates, such as mosquitoes and sea lice.[3][4][5] The three genera of Influenzavirus, which are identified by antigenic differences in their nucleoprotein and matrix protein infect vertebrates as follows:

Influenzavirus A infects humans, other mammals, and birds, and causes all flu pandemics Influenzavirus B infects humans and seals Influenzavirus C infects humans and pigs

Contents[hide]

1 Classification 2 Types o 2.1 Influenza A o 2.2 Influenza B o 2.3 Influenza C 3 Virology o 3.1 Morphology o 3.2 Genome o 3.3 Structure

3.4 Life cycle 4 Viability and disinfection 5 Vaccination and Prophylaxis 6 Referenceso

7 External links

[edit] ClassificationIn a phylogenetic-based taxonomy the "RNA viruses" includes the "negative-sense ssRNA viruses" which includes the Order "Mononegavirales", and the Family "Orthomyxoviridae" (among others). The genera-associated species and serotypes of Orthomyxoviridae are shown in the following table.Orthomyxoviridae Genera, Species, and Serotypes Genus Species (* indicates type species) Serotypes or Subtypes H1N1, H3N1, H5N1, H5N8, H7N2, H7N7, H1N2, H3N2, H5N2, H5N9, H7N3, H9N2, H2N2, H3N8, H5N3, H7N1, H7N4, H10N7 Hosts

Influenzavirus A Influenza A virus*

Human, pig, bird, horse

Influenzavirus B Influenza B virus* Influenzavirus C Influenza C virus* Isavirus Infectious salmon anemia virus* Thogoto virus* Thogotovirus Dhori virus

Human, seal Human, pig Atlantic salmon Tick, mosquito, mammal Batken virus, Dhori virus (including human)

Quaranfil virus, Johnston Atoll virus, Lake Chad virus

[edit] Types

There are four genera of influenza virus: Influenzavirus A, Influenzavirus B, Influenzavirus C and Ryanovirus. Each genus includes only one species, or type: Influenza A virus, Influenza B virus, and Influenza C virus, respectively. Influenza A and C infect multiple species, while influenza B almost exclusively infects humans.[6][7][edit] Influenza A Main article: Influenzavirus A

Influenza A viruses are further classified, based on the viral surface proteins hemagglutinin (HA or H) and neuraminidase (NA or N)... Sixteen H subtypes (or serotypes) and nine N subtypes of influenza A virus have been identified.

Diagram of influenza nomenclature.

Further variation exists; thus, specific influenza strain isolates are identified by a standard nomenclature specifying virus type, geographical location where first isolated, sequential number of isolation, year of isolation, and HA and NA subtype.[8][9] Examples of the nomenclature are:1. A/Brisbane/59/2007 (H1N1) 2. A/Moscow/10/99 (H3N2)

The type A viruses are the most virulent human pathogens among the three influenza types and causes the most severe disease. The serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:

H1N1 caused "Spanish Flu" in 1918, "Swine flu" in 2009.[10] H2N2 caused "Asian Flu". H3N2 caused "Hong Kong Flu". H5N1 is a pandemic threat. H7N7 has unusual zoonotic potential.[11] H1N2 is endemic in humans and pigs. H9N2, H7N2, H7N3, H10N7.

Flu pandemics[12] Name Year Deaths (millions) Subtype involved possibly H2N2 H1N1 H2N2 H3N2 H1N1

Asiatic 18891 (Russian) Flu 90 Spanish Flu Asian Flu Hong Kong Flu Swine Flu 191840 20 19571-1.5 58 19680.75 69 2009 - ...

[edit] Influenza B Main article: Influenzavirus B

Influenza B virus is almost exclusively a human pathogen, and is less common than influenza A. The only other animal known to be susceptible to influenza B infection is the seal.[13] This type of influenza mutates at a rate 2-3 times lower than type A[14] and consequently is less genetically diverse, with only one influenza B serotype.[6] As a result of this lack of antigenic diversity, a degree of immunity to influenza B is usually acquired at an early age. However, influenza B mutates enough that lasting immunity is not possible.[15] This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift), ensures that pandemics of influenza B do not occur.[16][edit] Influenza C Main article: Influenzavirus C

The influenza C virus infects humans and pigs, and can cause severe illness and local epidemics. [17] However, influenza C is less common than the other types and usually seems to cause mild disease in children.[18][19]

[edit] Virology

[edit] Morphology

Structure of the influenza virion. The hemagglutinin (HA) and neuraminidase (NA) proteins are shown on the surface of the particle. The viral RNAs that make up the genome are shown as red coils inside the particle and bound to Ribonuclear Proteins (RNPs).

The virion is pleomorphic, the envelope can occur in spherical and filamentous forms. In general the virus's morphology is spherical with particles 50 to 120 nm in diameter, or filamentous virions 20 nm in diameter and 200 to 300 (-3000) nm long. There are some 500 distinct spikelike surface projections of the envelope each projecting 10 to 14 nm from the surface with some types (i.e. hemagglutinin esterase (HEF)) densely dispersed over the surface, and with others (i.e. hemagglutinin (HA)) spaced widely apart. The major glycoprotein (HA) is interposed irregularly by clusters of neuraminidase (NA), with a ratio of HA to NA of about 4-5 to 1. Lipoprotein membranes enclose the nucleocapsids; nucleoproteins of different size classes with a loop at each end; the arrangement within the virion is uncertain. The nucleocapsids are filamentous and fall in the range of 50 to 130 nm long and 9 to 15 nm in diameter. They have a helical symmetry.[edit] Genome

Viruses of this family contain 6 to 8 segments of linear negative-sense single stranded RNA.[20] The total genome length is 12000-15000 nucleotides (nt). The largest segment 2300-2500 nt; of second largest 2300-2500 nt; of third 2200-2300 nt; of fourth 1700-1800 nt; of fifth 1500-1600 nt; of sixth 1400-1500 nt; of seventh 1000-1100 nt; of eighth 800-900 nt. Genome sequence has terminal repeated sequences; repeated at both ends. Terminal repeats at the 5'-end 12-13 nucleotides long. Nucleotide sequences of 3'-terminus identical; the same in genera of same family; most on RNA (segments), or on all RNA species. Terminal repeats at the 3'-end 9-11 nucleotides long. Encapsidated nucleic acid is solely genomic. Each virion may contain defective interfering copies.[edit] Structure For an in-depth example, see H5N1 genetic structure.

The following applies for Influenza A viruses, although other influenza strains are very similar in structure:[21] The influenza A virus particle or virion is 80-120 nm in diameter and usually roughly spherical, although filamentous forms can occur.[22] Unusually for a virus, the influenza A genome is not a single piece of nucleic acid; instead, it contains eight pieces of segmented negative-sense RNA (13.5 kilobases total), which encode 11 proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2).[23] The best-characterised of these viral proteins are hemagglutinin and neuraminidase, two large glycoproteins found on the outside of the viral particles. Neuraminidase is an enzyme involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles. By contrast, hemagglutinin is a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell.[24] The hemagglutinin (H) and neuraminidase (N) proteins are targets for antiviral drugs.[25] These proteins are also recognised by antibodies, i.e. they are antigens.[12] The responses of antibodies to these proteins are used to classify the different serotypes of influenza A viruses, hence the H and N in H5N1.[edit] Life cycle

Invasion and replication of the influenza virus. The steps in this process are discussed in the text.

Typically, influenza is transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus, and from infected birds through their droppings. Influenza can also be transmitted by saliva, nasal secretions, feces and blood. Infections occur through

contact with these bodily fluids or with contaminated surfaces. Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0 C (32 F), and indefinitely at very low temperatures (such as lakes in northeast Siberia). They can be inactivated easily by disinfectants and detergents.[26][27][28] The viruses bind to a cell through interactions between its hemagglutinin glycoprotein and sialic acid sugars on the surfaces of epithelial cells in the lung and throat (Stage 1 in infection figure). [29] The cell imports the virus by endocytosis. In the acidic endosome, part of the haemagglutinin protein fuses the viral envelope with the vacuole's membrane, releasing the viral RNA (vRNA) molecules, accessory proteins and RNA-dependent RNA polymerase into the cytoplasm (Stage 2).[30] These proteins and vRNA form a complex that is transported into the cell nucleus, where the RNA-dependent RNA transcriptase begins transcribing complementary positive-sense cRNA (Steps 3a and b).[31] The cRNA is either exported into the cytoplasm and translated (step 4), or remains in the nucleus. Newly-synthesised viral proteins are either secreted through the Golgi apparatus onto the cell surface (in the case of neuraminidase and hemagglutinin, step 5b) or transported back into the nucleus to bind vRNA and form new viral genome particles (step 5a). Other viral proteins have multiple actions in the host cell, including degrading cellular mRNA and using the released nucleotides for vRNA synthesis and also inhibiting translation of host-cell mRNAs.[32] Negative-sense vRNAs that form the genomes of future viruses, RNA-dependent RNA transcriptase, and other viral proteins are assembled into a virion. Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. The vRNA and viral core proteins leave the nucleus and enter this membrane protrusion (step 6). The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7).[33] As before, the viruses adhere to the cell through hemagglutinin; the mature viruses detach once their neuraminidase has cleaved sialic acid residues from the host cell.[29] After the release of new influenza virus, the host cell dies. Since RNA proofreading enzymes are absent, the RNA-dependent RNA transcriptase makes a single nucleotide insertion error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA. Hence, nearly every newly-manufactured influenza virus will contain a mutation in its genome.[34] The separation of the genome into eight separate segments of vRNA allows mixing (reassortment) of the genes if more than one variety of influenza virus has infected the same cell (superinfection). The resulting alteration in the genome segments packaged in to viral progeny confers new behavior, sometimes the ability to infect new host species or to overcome protective immunity of host populations to its old genome (in which case it is called an antigenic shift).[12]

[edit] Viability and disinfectionMammalian influenza virus tend to be labile, but can survive several hours in mucus.[35] Avian influenza virus can survive for 100 days in distilled water at room temperature, and 200 days at 17 C (63 F). The avian virus is inactivated more quickly in manure, but can survive for up to 2 weeks in feces on cages. Avian influenza viruses can survive indefinitely when frozen.[35] Influenza viruses are susceptible to bleach, 70% ethanol, aldehydes, oxidizing agents, and

quaternary ammonium compounds. They are inactivated by heat of 133 F (56 C) for minimum of 60 minutes, as well as by low pH