Orthomyxoviruses -> (-) strand RNA genome Influenza Types -> A/B: Effects humans (causes pandemics) -> C: Mild illness in humans -> D: effects cattle mostly Influenza A Structure -> highly pleomorphic -> Most common - spherical or ovoid (D = 80-120nm) -> Bilipid envelope + viral glycoprotiens (spike proteins ~500) embedded in membrane Glycoproteins Hemagglutinin (H) - 5 Tri-mer of identical subunits Digests Salacylic Acid, to detach from host cell (after replication is over) Neuraminidase (N) - 1 Tetra-mer or identical subunits Other envelop proteins M1 M2 Lines inside of lipid envelope Helps in assembly pf necleocaspid, envelope and glycoprotiens. (late stage) lon Chanel for H+ (Out -> In) Addidification, triggers viral genome to be released from M1 Genome -> 10 Genes on 8 (-) sense RNA mol. -> Each Coated with nucleoprotien (NP) -> Each has own RNA Pol complex (PA, PB1, PB2) -> Each segment is replicated and transcribed independently Genome Segments = RiboNucleoProtiens (RNPs) -> (-) RNA -> Nucleoprotien (NP) -> RNA-dependant polymerase complex (PA, PB1, PB2) -> 1 NP : 20 Nucleotides -> Replicate in the host nucleus -> RNPs are assembled first in the nucleus and completed in cytoplasm
Influenza A - Subtypes -> H (1-18) -> N (1-11) -> Potential Combinations: 198 -> Naturally Occaring Combinations: 131 -> Currently most in circulation: A(H1N1) & A(H3N2) Naming the Influenza Virus Understanding the naming of flu viruses Host Range - Virus type ! Strain number 1 Virus subtype A / Sydney / 05 / 97 (H3N2) Place virus isolated 1 Year isolated Humans (H1-H3, H5, H7, H10) Horses (H3, H7) Poultry (H1-H13) ------- Pigs (H1-H7, H10, H11) Dogs (H3) Cats (H1, H5) Marine Mammals (H1, H3, H4, H7, H10, H13) Wild birds (H1-H16) Bats (H17, H18) Replication Cycle BINDING OF HA GLYCOPROTEIN TO SIALIC ACIDS AT CELL SURFACE Ribonucleoprotein FUSION WITH VESICLE WALL UPTAKE VIA CLATHRIN- COATED AND OTHER VESICLES ACIDIFICATION EXPOSES HA2 FUSION PEPTIDE M2 PROTEIN MEDIATES ENTRY OF H+ IONS INTO VIRION Oligomerization HA NA HA NA M2 Genomic RNA (as ribonucleoprotein) 5' capped primers from host mRNAs NP Antigenomic RNAs (cRNAs) mRNAs NP SPLICING Genomic RNAs Glycosylation of HA and NA in Golgi Proteins M1 ASSEMBLY INTO RIBONUCLEOPROTEIN M proteins Viral HA and NA glycoproteins Lipid raft BUDDING RELEASE FROM CELL BY NA GLYCOPROTEIN (Virions may be filamentous)
Entry 1- Attachment of Virus Particle - Virus enters respiratory tract - Initial low affinity interaction w/ SA on mucoprotiens on epithelial cells - Additive effect of many interactions - Virus enters epithelial cell by receptor-mediaded endocytosis 2 - Receptor Mediated Endocytosis - Protease secreted by Clara cells of host bronchilar epothlium - Protiease secreted into the mucus layer of respiratory tract - H proteins are cleaved by protease (typtase Clara): Ho -> H1 + H2 - H2 - N-terminal has fusion peptide - H1 - Binds to SA - H2 - Stays integrated with the bilayer 3 - Fusion of Viral Envelope + Endosome Membrane - Endosome Acidification (M2) -> Conformational Change in H