Marsh GA, Rabadán R, Levine AJ, Palese P.. Highly conserved regions of the influenza A virus polymerase gene segments are critical for efficient vRNA packaging. J Virol. 2007 Dec 19
The genome of the Influenza A virus is composed of eight different segments of negative sense RNA. These eight segments are incorporated into budding virions in an equimolar ratio through a mechanism that is not fully understood. Two different models have been proposed for packaging the viral ribonucleoproteins into newly assembling virus particles: the random incorporation model and the selective incorporation model. In the last few years increasing evidence from many different laboratories has been accumulated that supports the selective incorporation model. In particular, different groups have shown that some large viral RNA regions within the coding sequences at both the 5´ and 3´ ends of almost every segment are sufficient for packaging foreign RNA sequences. If the packaging regions are crucial for the viability of the virus we would expect them to be conserved. Using large scale analysis of Influenza A virus sequences, we developed a method of identifying RNA conserved regions whose conservation cannot be explained by population structure or amino acid conservation. Interestingly, the conserved sequences are located within the regions identified as important for efficient packaging. By utilizing influenza virus reverse genetics we have rescued mutant viruses containing synonymous mutations within these highly conserved regions. Packaging of viral RNAs in these viruses was analyzed by reverse transcription using a universal primer and quantitative PCR for individual segments. Employing this approach we have identified regions in the polymerase gene segments that if mutated result in reductions of more than 90% in the packaging of that particular polymerase viral RNA. Reductions in the packaging of a polymerase viral RNA frequently resulted in reductions of other viral RNAs as well, and the results form a pattern of hierarchy of segment interactions. This work provides further evidence for a selective packaging mechanism for influenza A viruses, demonstrating that these highly conserved regions are important for efficient packaging.
See Also:
- http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=18094182&dopt=AbstractPlus
Latest articles in those days:
- Epitopes in the HA and NA of H5 and H7 avian influenza viruses that are important for antigenic drift 1 days ago
- Assessment of CD8+ T-cell mediated immunity in an influenza A(H3N2) human challenge model in Belgium: a single centre, randomised, double-blind phase 2 study 1 days ago
- Dual N-linked glycosylation at residues 133 and 158 in the hemagglutinin are essential for the efficacy of H7N9 avian influenza virus like particle vaccine in chickens and mice 1 days ago
- Effect of human H3N2 influenza virus reassortment on influenza incidence and severity during the 2017-18 influenza season in the USA: a retrospective observational genomic analysis 1 days ago
- [preprint] Virome Sequencing Identifies H5N1 Avian Influenza in Wastewater from Nine Cities 1 days ago
[Go Top] [Close Window]