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Highly conserved regions of influenza a virus polymerase gene segments are critical for efficient viral RNA packaging.

Highly conserved regions of influenza a virus polymerase gene segments are critical for efficient viral RNA packaging. Research Abstract Details 

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  • Highly conserved regions of influenza a virus polymerase gene segments are critical for efficient viral RNA packaging. Abstract Text:

    glenn a marshGlenn A Marsh,raúl rabadánRaúl Rabadán,arnold j levineArnold J Levine,peter palesePeter Palese,glenn a marshGlenn A Marsh, ,arnold j levineArnold J Levine,peter palesePeter Palese,

    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 that supports the selective-incorporation model has been accumulated. 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 conserved RNA 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 level of 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.

    Highly conserved regions of influenza a virus polymerase gene segments are critical for efficient viral RNA packaging. Publishing Authors By Initials

    ga marshGA Marsh,r rabadánR Rabadán,aj levineAJ Levine,p paleseP Palese,ga marshGA Marsh,r R ,aj levineAJ Levine,p paleseP Palese,

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    Highly conserved regions of influenza a virus polymerase gene segments are critical for efficient viral RNA packaging. Journal Published:

    PUBLICATION TYPE: Research Support, U.S. Gov't,

    Journal: Journal of virology

    VOLUME: 82

    Page Numbers: 2295-304

    Journal Abbreviation: J. Virol.

    ISSN: 1098-5514

    DAY: 19

    MONTH: 12

    YEAR: 2007

    Highly conserved regions of influenza a virus polymerase gene segments are critical for efficient viral RNA packaging. Information

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    LANGUAGE: eng

    NlmUniqueID: 113724

    Highly conserved regions of influenza a virus polymerase gene segments are critical for efficient viral RNA packaging. Keywords Mesh Terms:

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    Grant and Affiliation Information for Highly conserved regions of influenza a virus polymerase gene segments are critical for efficient viral RNA packaging.

    AFFILIATION: Department of Microbiology, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIAID

    GRANT: UO1AI070469

    ACRONYM: AI

    MEDLINETA: J Virol

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