Hello! I see that everyone is concerned about the swine flu we are having and many people would like to know more about it. I took a Virology course this year and I believe it is important for the public to be educated about influenza virus in general, so I'd decided to share my notes about influenza virus with all of you. Hope my notes would answer some of the questions you may have----the notes may be too technical for the general public but I hope they can be helpful.
Good luck everyone!
---Influenza:
1. Classification: Group V ((-)ssRNA), Orthomyxoviridae
2. Host range: Humans, birds (reservoirs), pigs, and horses. Human flu distribution world-wide, year-round at tropics and winter at temperate.
3. Physical and other properties: Spherical enveloped (filamentous form also possible), virus particles enclosed in a host-derived lipid envelope, and a matrix exists under the envelope.
4. Genetics: segmented neg-sense ssRNA genome. The viral RNA is associated with another protein to form a nucleoprotein (NP). In types A and B, genomes consist of eight RNA segments while in type C the genome consists of seven RNA segments. Genomes change over time by accumulating point mutations and reassorting RNA segments with others. Viruses undergo continuous variation, with A subjects to antigenic shift (significant changes an all kinds of cross-species variations) and B and C subject to antigenic drift (point mutations). For A, RNA is circular due to a terminal panhandle structure which is stabilized by base-pairing between 3鈥?and 5鈥?ends of the RNA segments. Type A evolves faster than the other types (B and C) as it can reassort with avian flu viruses, thus mixing the viral gene pools.
5. Gene expression, transcription/translation/replication: Transcription takes place in the cell nucleus. The virus shows a cap-snatching mechanism during transcription and uses cellular mRNA cap to cap their own mRNA. The viral RNA complex (PB1, PB2, and PA, and they are RNA-dep RNA polymerizing) uses the viral RNP as a template for synthesis of two types of RNA: 1) a complementary-sense RNA copy (cRNA) to produce a full-length viral RNA (vRNA), and 2) a viral mRNA. The cRNA and vRNA have similar promoter sequences and the sequences are highly conserved. The vRNAs form a panhandle structure, which is believed to contain signals for polyadenation and packaging of vRNAs. These vRNAs are not only used as a template for replication, but also for the synthesis of mRNAs. For translation, the RNA segment 7 of type A encodes M1 and M2. M2 is made by translation of a M1 spliced mRNA, and during this splicing there is a frameshift, and other two proteins, NS1 and NS2, also result from unspliced/spliced forms of RNA segment 8 of types A and B. Another interesting feature of influenza translation is that following the stop codon (UAA) in the M1 protein, cellular ribosomes are able to reinitiate translation by using an AUG codon that overlaps this stop signals by shifting ORF by one nucleotide. Post-translational processing of the HA includes a removal of a signal sequence from the N-terminus, leading to HA attachment to rough ER membrane before being cleaved. The cleavage into HA1 and HA2 and the insertion of these two (with a disulfide link) into host cell membrane is essential for HA fusogenic activity.
6. Serology, relationships, strains, variability, etc: Three strains: A, B and C, and they are antigenically distinct on the basis of their NP. Type A commonly causes respiratory illness in humans, pigs, horses. Three HA subtypes have been identified in humans, two in pigs and horses, while all 14 subtypes have been found in birds. Birds do not usually suffer diseases from influenza, instead acting as reservoirs. Type B occur only in humans and type C occur in both humans and pigs.
7. Major proteins and notable components: There are two kinds of surface spike proteins: hemagglutinin (HA) which agglutinates erythrocytes, and an enzyme neuraminidase (NA) which acts to release the virus from the cells. A third capsid protein (M) forms a matrix below the lipid envelope. The viral RNA is associated with another protein to form a nucleoprotein (NP). The polymerase complex is composed of three parts: PB1, PB2, and PA. There is also a proton pump to aid uncoating.
8. Attachment and Entry: HA attaches the virus to the cell. Acidification inside the endosome induces a HA conformational change, leading to an eventual fusion of the viral envelope with the endosome membrane, thereby releasing the viral nucleocapsid into the cell cytoplasm.
9. Assembly and Release: vRNA鈥檚 ends contain cis signals for packaging, and each viral particle will package 11-12 RNA segments, with the segments randomly taken from a pool of the 8 different vRNAs. Only less than 10% of particles contain complete genomes and are infectious. For assembly, M1 enters the nucleus and appears to be responsible for transport of viral RNPs into the cytoplasm. In the cytopl The notes were too long to got cut off.... see part 2 if you want to learn the rest. You are the man!!!! LOL
Thanks so much for sharing this information with us--what ever it is --you just said--I am sure is very educational LOL
You just make me laugh some times !!!! LOL thanks. |
