Orthomyxoviruses
Terms
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- Orthomyxoviruses
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-spherical or ovoid enveloped
-buds
-2 major envelope surface glycoproteins: NA and HA
-ssRNA (-) all within matrix
-helical nucleocapsid made of nucleocapsid protein - Neuraminidase
-
-major envelope surface glycoprotein
-orthomyxoviruses
-used to distinguish subtype of virus within subtype (influenza A H1N1) - Hemagglutinin
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-major envelope surface glycoprotein
-orthomyxoviruses
-used to distinguish subtype of virus within subtype (influenza A H1N1) - Influenza A
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-widespread various animals
-genomes into 8 pieces, each for different protein, allowing to recombine when two subtypes co-infect
-13500 nt genome
-most clinically important subtype
-imported and grows into episodic epidemic (Dec-Mar)
-large genetic pool, recombination easier
-highly variable antigenic properties for survival - Influenza B
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-only humans
-genomes into 8 pieces, each for different protein
-not much recombination, smaller genomic pool (only humans) - Influenza C
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-only humans
-7 segments genome
-not much recombination, smaller genomic pool (only humans) - Thogotovirus
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-tick-borne
-not well characterised
-6 segments genome - Matrix
- -composed of matrix protein M1
- Mouse tracheal cells experiment
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-shows influenza destroys first line of defese against inhaled pathogens (bacteria)
-through desquamation of ciliated epithelium, virus facilitates bacterial entry - Desquamation
- -replicating virus in and thus killing round mucous-secreting cells and ciliated upwards beating cells of upper tracheal epithelium
- Hemophilus influenzae
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-gram negative coccobacillus
-cause of 1918 Spanish flu pandemic
-human experiments show maximal illness at same time maximal viral sheeding - Flu (A) symptoms
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-due to produciton of interferon, cytokines and repsonse factros in response to viral replication
-1-4 days after infection - Flu pandemics
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-10-50 years irregularly
-1918 Spanish
-1957 Asian
-1967 Hong Kong - Natural Immunity against flu
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-against NA and HA
-no cross immunity of subtypes
-protective immunity that is not lifelong since glycoproteins regularly undergo antigenic drift - Antigenic Drift
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-mutational antigenicity
-1% change in AA sequence glycoprotines per year through random point mutations in antigenic domains - Antigenic Shift
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-every decade or so happens to one glycoprotein
-through genetic recombination with animal influenza subtypes
-potential to be pandemic or epidemic - Antigenic diversity
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-increased by virally encoded error-prone RNA dependedent RNA polymerase
-high nucleotide or aa sequence diveristy in WT viral particles - Spanish flu
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-1918
-20 million deaths
-H1N1
-avian/human recombinant formed in infected swine cell
-cyclic shift allowed influneza to remain pathogenic
-disappeared in 1956 along with appearance H2N2 - 1880 Flu
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-H3N2
-cyclic shift to 1968 but most population in flu from 1880 had died - Asian flu 1
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-1947
-H1N1 - Asian flu 2
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-1957
-H2N2 - Hong Kong flu
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-1968
-H3N2
-due to antigenic shift - Swine flu scare
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-1976
-H3N2+H1N1
-deadly flu containing Hswine thought to be new recombitnant
-actually no recombination
-human-human transmission are low - Cross-specicies infection
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-by influenza usualyl does not occur unless large inoculate
-due to host specificity therefore does not occur - Avian flu
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-resevoirs, not affected
-H5N1
-humans have partial immunity to N1, no immunity to H5
-although all carry H6 and N1, rest genes are bird genes
-jumped species barrier due to proximity
-66 cases in humans, no human-human transmission
-gets into human respiratory tract, fear of it encoutnering human influenza and recombining making easy spread human to human and therefore pandemic - Influenza A genome
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-3 largest segments: polymerase proteins
-4th: hemagglutinin
-5th: nucleoprotein
-6th: neuraminidase
-7th: matrix protein (smaller)
-8th: major non structural protein NS1 (smaller)
-splicing mechanism makes sub genomic mRNA's encoding two small addition proteins