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Influenza Virus Gus Kousoulas, Ph.D. BIOMMED http://biommed.lsu.edu Families of RNA viruses Common Properties myxo- mucous tropic • orthomyxovirus = influenza • (-) polarity ssRNA • enveloped viruses • encapsidates RNA polymerase • causes worldwide disease • responsible for > 10% work/school absence • acute infections and diseases • known since 1500’s Orthomyxovirus: classification Three types • Influenza A - highly variable - infects humans, birds, pigs, horses, seals - most prevalent human virus - cause of most human epidemics • Influenza B - infects only animals • Influenza C - infects human and swine - antigenic stable, only mild illness Avian Influenza • Avian influenza is an infectious disease of birds caused by type A strains of the influenza virus. • Infection causes a wide spectrum of symptoms in birds, ranging from mild illness to a highly contagious and rapidly fatal disease resulting in severe epidemics. The latter is known as “highly pathogenic avian influenza”. This form is characterized by sudden onset, severe illness, and rapid death, with a mortality that can approach 100%. • To date, all outbreaks of the highly pathogenic form have been caused by influenza A viruses of subtypes H5 and H7. • Avian influenza viruses do not normally infect species other than birds and pigs. The first documented infection of humans with an avian influenza virus occurred in Hong Kong in 1997, when the H5N1 strain caused severe respiratory disease in 18 humans, of whom 6 died. Avian Influenza • An outbreak of highly pathogenic H7N7 avian influenza, which began in the Netherlands in February 2003, caused the death of one veterinarian two months later, and mild illness in 83 other humans. • In January 2004, laboratory tests confirmed the presence of H5N1 avian influenza virus in human cases of severe respiratory disease in the northern part of Viet Nam. • Recently, virulent asian influenza strains were detected in dead chickens and specimens of young patients that died from influenza- related complications (Turkey). • Based on historical patterns, influenza pandemics can be expected to occur, on average, three to four times each century when new virus subtypes emerge and are readily transmitted from person to person. In the 20th century, the great influenza pandemic of 1918–1919, which caused an estimated 40 to 50 million deaths worldwide, was followed by pandemics in 1957–1958 and 1968–1969. Diagram of influenza virus (Orthomyxovirus) Genome- segmented RNA Capsid- nucleoprotein Nucleocapsid- helical Matrix proteins- 1, 2 Envelope Glycoproteins- NA, HA Structural proteins Non-structural proteins Structure: viral components • Hemagglutinin (HA) * - HA0 cleaved to become HA1, HA2 - Naturally occurs as trimer - Sialic acid is cellular receptor - Responsible for membrane fusion • Neuraminidase (NA)* - naturally occurs as tetramer - cleaves sialic acid at exit/egress Orthomyxovirus: Classification • How to name an influenza virus? Type ABC/ City/ strain #/ year isolated/glycoproteins HA(1-14) NA (1-9) e.g. A/ HongKong/ 03/ 1968/ H3N2 • Worldwide epidemics = pandemics - 1918-19 influenza pandemic caused 20 million deaths - 1947, 1957 (Asian flu); 1968, 1977, 1987 Portal of Entry of Influenza Virus Inhalation of respiratory secretions Influenza virus genetic variation Antigenic drift . point mutations in RNA encoding HA or NA . results in new antigenic sites . occurs frequently- yearly changes . no correction for errors made by viral RNA polymerase . allows virus to avoid mucosal IgA antibodies Antigenic shift . reassortment when two influenza strains infect the same cell e.g. avian and human virus infect same cell . cause of periodic new influenza epidemics . completely new set of HA and NA can be in progeny virus . pandemics occurs typically every 10-14 years Influenza virus variation Antigenic shift Antigenic drift Impact of Influenza Pandemics • 1918-19 Spanish Flu (H1N1) • 20 to 40 million deaths worldwide • At least 550,000 US deaths (only 80% of pop. included in vital statistics data) • 1957-58 Asian Flu (H2N2) • ~70,000 US deaths • 1968-69 Hong Kong Flu (H3N2) • ~34,000 US deaths • Current interpandemic influenza • ~36,000 US deaths • >200,000 hospitalizations • "Bird Flu" Similar to Deadly 1918 Flu, Gene Study Finds • Brian Handwerk for National Geographic News • October 5, 2005 • Scientists have reconstructed the genetic code of the deadly 1918 "Spanish flu," which swept the globe and killed an estimated 20 to 40 million people. Among their findings: The 1918 virus strain developed in birds and was similar to the "bird flu" that today has spurred fears of another worldwide epidemic. Influenza control and prevention Yearly vaccine available- inactivated virus . ~70% protective for a given year Current vaccine made in chicken embryo . cocktail of circulating human strains from previous year . purify and formalin inactivate virus . each dose =10 billion virus particles . takes time to prepare . given in one dose before flu season New vaccine options . HA and NA subunit (~15 μg of HA) . “cold adapted” live attenuated virus (Flu-Mist) (UM SPH Dr. Masaab), FDA approved Influenza control and prevention • Who should receive vaccine? – Health care workers – High risk individuals . elderly > 65 years . people with underlying diseases (chronic lung disease, asthma, diabetes, heart disease) Current conventional vaccines will not protect against avian virulent strains!!!
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