Chimeric Influenza A Viruses with a Functional Influenza B Virus Neuraminidase or Hemagglutinin

A, Flandorfer; Garcı́a-Sastre, Adolfo; Basler, Christopher F.; Palese, Peter

doi:10.1128/jvi.77.17.9116-9123.2003

Cited by 32 publications

(26 citation statements)

References 30 publications

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“…Previously, we successfully generated type A/B chimeric virus, which contained type B HA in a type A virus background, indicating functional compatibility between type A and B HA glycoproteins (Horimoto et al, 2003). In addition, two studies have reported that type B NA can replace the function of type A NA (Ghate and Air, 1999;Flandorfer et al, 2003). Taken together with our current findings, the lack of intertypic reassortants cannot be explained by incompatibilities at the protein level.…”

Section: Discussionsupporting

confidence: 83%

Limited compatibility between the RNA polymerase components of influenza virus type A and B

Iwatsuki‐Horimoto

Hatta

et al. 2008

Virus Research

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Reassortants between type A and B influenza viruses have not been detected in nature, although both viruses co-circulate in human populations. One explanation for this may be functional incompatibility of RNA transcription and replication between type A and B viruses. To test this possibility, we constructed type A/B mosaic polymerase machinery, containing PB2, PB1, PA and nucleoprotein from each of the two virus types, and assessed their polymerase activities with a type A promoter in a reporter assay. Type B polymerase machinery containing homologous components was functional with the type A promoter albeit to various extents depending on the segments from which the regions downstream of the promoter sequence were derived, indicating functional compatibility between the type A promoter and B polymerase machinery. However, all of the A/B mosaic polymerase machinery, except that containing PA from a type A and the others from a type B virus strain, did not function with the type A promoter, indicating limited compatibility among polymerase components of both types. Taken together, these data suggest that incompatibility among components of the polymerase machinery for RNA transcription and replication alone is not responsible for the lack of heterotypic reassortants.

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Section: Discussionsupporting

confidence: 83%

Limited compatibility between the RNA polymerase components of influenza virus type A and B

Iwatsuki‐Horimoto

Hatta

et al. 2008

Virus Research

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“…Parental MDCK and MDCK-HA cells (10 6 cells, 6-well plate format) were trypsinized and stained in suspension as previously described (4). Briefly, cells were washed and incubated with 31C2, PY102, NR-3165, rabbit anti-B/Lee PAb (V-63, 1:1,000) (18), and mouse anti-B/Yam MAb (MAb 15B6, 1:1 of hybridoma TCS) (18) for 30 min at 4°C. After washing 3 times in staining buffer (1ϫ PBS with 5% FBS).…”

Section: Methodsmentioning

confidence: 99%

“…The mechanism governing this segregation is unclear, but intertypic incompatibility at the protein or vRNA level has been hypothesized to be an underlying factor (14)(15)(16). Although recombinant chimeric influenza A/B viruses have been created, suggesting that portions of influenza B virus glycoproteins can replace the function of influenza A virus glycoproteins, substantial genetic modifications of the polypeptides were required for their successful rescue (17)(18)(19). Additionally, the RNA-dependent RNA polymerase (RdRp) of influenza A or B virus has been shown to transcribe genes flanked by the heterotypic promoter sequences (20)(21)(22) found in the terminal noncoding regions (NCRs) of each vRNA (23,24).…”

mentioning

confidence: 99%

Influenza A and B Virus Intertypic Reassortment through Compatible Viral Packaging Signals

Baker

Nogales

Finch

et al. 2014

J Virol

104

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Influenza A and B viruses cocirculate in humans and together cause disease and seasonal epidemics. These two types of influenza viruses are evolutionarily divergent, and exchange of genetic segments inside coinfected cells occurs frequently within types but never between influenza A and B viruses. Possible mechanisms inhibiting the intertypic reassortment of genetic segments could be due to incompatible protein functions of segment homologs, a lack of processing of heterotypic segments by influenza virus RNA-dependent RNA polymerase, an inhibitory effect of viral proteins on heterotypic virus function, or an inability to specifically incorporate heterotypic segments into budding virions. Here, we demonstrate that the full-length hemagglutinin (HA) of prototype influenza B viruses can complement the function of multiple influenza A viruses. We show that viral noncoding regions were sufficient to drive gene expression for either type A or B influenza virus with its cognate or heterotypic polymerase. The native influenza B virus HA segment could not be incorporated into influenza A virus virions. However, by adding the influenza A virus packaging signals to full-length influenza B virus glycoproteins, we rescued influenza A viruses that possessed HA, NA, or both HA and NA of influenza B virus. Furthermore, we show that, similar to single-cycle infectious influenza A virus, influenza B virus cannot incorporate heterotypic transgenes due to packaging signal incompatibilities. Altogether, these results demonstrate that the lack of influenza A and B virus reassortants can be attributed at least in part to incompatibilities in the virus-specific packaging signals required for effective segment incorporation into nascent virions. IMPORTANCEReassortment of influenza A or B viruses provides an evolutionary strategy leading to unique genotypes, which can spawn influenza A viruses with pandemic potential. However, the mechanism preventing intertypic reassortment or gene exchange between influenza A and B viruses is not well understood. Nucleotides comprising the coding termini of each influenza A virus gene segment are required for specific segment incorporation during budding. Whether influenza B virus shares a similar selective packaging strategy or if packaging signals prevent intertypic reassortment remains unknown. Here, we provide evidence suggesting a similar mechanism of influenza B virus genome packaging. Furthermore, by appending influenza A virus packaging signals onto influenza B virus segments, we rescued recombinant influenza A/B viruses that could reassort in vitro with another influenza A virus. These findings suggest that the divergent evolution of packaging signals aids with the speciation of influenza A and B viruses and is in part responsible for the lack of intertypic viral reassortment.

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“…Chimeric influenza A viruses possessing the HA and NA genes of an influenza B virus have been generated previously by us (12) and others (13). Here, we therefore tested our recently developed influenza A high-yield vaccine candidate (9) with influenza B virus HA and NA genes.…”

Section: Resultsmentioning

confidence: 99%

Development of high-yield influenza B virus vaccine viruses

Ping

Lopes

Kawaoka

2016

Proc. Natl. Acad. Sci. U.S.A.

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The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six “internal” influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production.

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Chimeric Influenza A Viruses with a Functional Influenza B Virus Neuraminidase or Hemagglutinin

Abstract: Reassortment of influenza

Cited by 32 publications

References 30 publications

Limited compatibility between the RNA polymerase components of influenza virus type A and B

Limited compatibility between the RNA polymerase components of influenza virus type A and B

Influenza A and B Virus Intertypic Reassortment through Compatible Viral Packaging Signals

Development of high-yield influenza B virus vaccine viruses

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