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Evidence for a novel gene associated with human influenza A viruses.

ABSTRACT: BACKGROUND:Influenza A virus genomes are comprised of 8 negative strand single-stranded RNA segments and are thought to encode 11 proteins, which are all translated from mRNAs complementary to the genomic strands. Although human, swine and avian influenza A viruses are very similar, cross-species infections are usually limited. However, antigenic differences are considerable and when viruses become established in a different host or if novel viruses are created by re-assortment devastating pandemics may arise. RESULTS:Examination of influenza A virus genomes from the early 20th Century revealed the association of a 167 codon ORF encoded by the genomic strand of segment 8 with human isolates. Close to the timing of the 1948 pseudopandemic, a mutation occurred that resulted in the extension of this ORF to 216 codons. Since 1948, this ORF has been almost totally maintained in human influenza A viruses suggesting a selectable biological function. The discovery of cytotoxic T cells responding to an epitope encoded by this ORF suggests that it is translated into protein. Evidence of several other non-traditionally translated polypeptides in influenza A virus support the translation of this genomic strand ORF. The gene product is predicted to have a signal sequence and two transmembrane domains. CONCLUSION:We hypothesize that the genomic strand of segment 8 of encodes a novel influenza A virus protein. The persistence and conservation of this genomic strand ORF for almost a century in human influenza A viruses provides strong evidence that it is translated into a polypeptide that enhances viral fitness in the human host. This has important consequences for the interpretation of experiments that utilize mutations in the NS1 and NEP genes of segment 8 and also for the consideration of events that may alter the spread and/or pathogenesis of swine and avian influenza A viruses in the human population.

SUBMITTER: Clifford M

PROVIDER: S-EPMC2780412 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Evidence for a novel gene associated with human influenza A viruses.

Clifford Monica M Twigg James J Upton Chris C

Virology journal 20091116

<h4>Background</h4>Influenza A virus genomes are comprised of 8 negative strand single-stranded RNA segments and are thought to encode 11 proteins, which are all translated from mRNAs complementary to the genomic strands. Although human, swine and avian influenza A viruses are very similar, cross-species infections are usually limited. However, antigenic differences are considerable and when viruses become established in a different host or if novel viruses are created by re-assortment devastati ...[more]

PMID: 19917120

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Project description:Influenza B virus (IBV) undergoes seasonal antigenic drift more slowly than influenza A virus, but the reasons for this difference are unclear. While the evolutionary dynamics of influenza viruses play out globally, they are fundamentally driven by mutation, reassortment, drift, and selection at the level of individual hosts. These processes have recently been described for influenza A virus, but little is known about the evolutionary dynamics of IBV during individual infections and transmission events. Here, we define the within-host evolutionary dynamics of IBV by sequencing virus populations from naturally infected individuals enrolled in a prospective, community-based cohort over 8,176 person-seasons of observation. Through analysis of high depth-of-coverage sequencing data from samples from 91 individuals with influenza B, we find that IBV accumulates lower genetic diversity than previously observed for influenza A virus during acute infections. Consistent with studies of influenza A viruses, the within-host evolution of IBVs is characterized by purifying selection and the general absence of widespread positive selection of within-host variants. Analysis of shared genetic diversity across 15 sequence-validated transmission pairs suggests that IBV experiences a tight transmission bottleneck similar to that of influenza A virus. These patterns of local-scale evolution are consistent with the lower global evolutionary rate of IBV.IMPORTANCE The evolution of influenza virus is a significant public health problem and necessitates the annual evaluation of influenza vaccine formulation to keep pace with viral escape from herd immunity. Influenza B virus is a serious health concern for children, in particular, yet remains understudied compared to influenza A virus. Influenza B virus evolves more slowly than influenza A virus, but the factors underlying this are not completely understood. We studied how the within-host diversity of influenza B virus relates to its global evolution by sequencing viruses from a community-based cohort. We found that influenza B virus populations have lower within-host genetic diversity than influenza A virus and experience a tight genetic bottleneck during transmission. Our work provides insights into the varying dynamics of influenza viruses in human infection.

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Evidence for a novel gene associated with human influenza A viruses.

Publications

Evidence for a novel gene associated with human influenza A viruses.

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