PB1-F2 Finder: scanning influenza sequences for PB1-F2 encoding RNA segments

DeLuca, David S.; Keskin, Derin B.; Zhang, Guanglan; Reinherz, Ellis L.; Brusic, Vladimir

doi:10.1186/1471-2105-12-s13-s6

Cited by 6 publications

(3 citation statements)

References 10 publications

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“…Additionally, S31 was found in M2 proteins in 191 H6 viruses, indicating no resistance to amantadine [ 67 ]. They also discovered that the expression of the PB1-F2 protein was blocked in 52.0% of the analysed H6 isolates, indicating the potentially variable virulence [ 97 , 98 , 99 , 100 ].…”

Section: Adaptation and Mutations In H6nx Virusesmentioning

confidence: 99%

The Evolution, Spread and Global Threat of H6Nx Avian Influenza Viruses

Everest

Hill

Daines

et al. 2020

Viruses

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Avian influenza viruses of the subtype H6Nx are being detected globally with increasing frequency. Some H6Nx lineages are becoming enzootic in Asian poultry and sporadic incursions into European poultry are occurring more frequently. H6Nx viruses that contain mammalian adaptation motifs pose a zoonotic threat and have caused human cases. Although currently understudied globally, H6Nx avian influenza viruses pose a substantial threat to both poultry and human health. In this review we examine the current state of knowledge of H6Nx viruses including their global distribution, tropism, transmission routes and human health risk.

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Section: Adaptation and Mutations In H6nx Virusesmentioning

confidence: 99%

The Evolution, Spread and Global Threat of H6Nx Avian Influenza Viruses

Everest

Hill

Daines

et al. 2020

Viruses

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“…When looking at the prevalence of a functional PB1-F2 in strains of various origins, its expression appears unequally distributed: for example 96% of avian strains encodes a full-length PB1-F2 while only 7% of human H1N1 isolates express a functional PB1-F2 [22] , [23] . Thus, several reports suggest that the loss of a functional PB1-F2 could be beneficial for the virus when it crosses the species barrier to spread through humans [22] , [24] – [26] . Consequently, the loss of PB1-F2 could be an adaptation process of the virus to mammalian hosts in order to confer optimized replicative efficiencies and viral fitness [27] .…”

Section: Introductionmentioning

confidence: 99%

PB1-F2 Attenuates Virulence of Highly Pathogenic Avian H5N1 Influenza Virus in Chickens

et al. 2014

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Highly pathogenic avian influenza virus (HPAIV) is a permanent threat due to its capacity to cross species barriers and generate severe infections and high mortality in humans. Recent findings have highlighted the potential role of PB1-F2, a small accessory influenza protein, in the pathogenesis process mediated by HPAIV in mammals. In this study, using a recombinant H5N1 HPAIV (wt) and its PB1-F2-deleted mutant (ΔF2), we studied the effects of PB1-F2 in a chicken model. Unexpectedly, when using low inoculation dose we observed that the wt-infected chickens had a higher survival rate than the ΔF2-infected chickens, a feature that contrasts with what is usually observed in mammals. High inoculation dose had similar mortality rate for both viruses, and comparison of the bio-distribution of the two viruses indicated that the expression of PB1-F2 allows a better spreading of the virus within chicken embryos. Transcriptomic profiles of lungs and blood cells were characterized at two days post-infection in chickens inoculated with the wild type (wt) or the ΔF2 mutant viruses. In lungs, the expression of PB1-F2 during the infection induced pathways related to calcium signaling and repressed a large panel of immunological functions. In blood cells, PB1-F2 was associated with a gene signature specific for mitochondrial dysfunction and down-modulated leucocytes activation. Finally we compared the effect of PB1-F2 in lungs of chickens and mice. We identified that gene signature associated to tissue damages is a PB1-F2 feature shared by the two species; by contrast, the early inhibition of immune response mediated by PB1-F2 observed in chickens is not seen in mice. In summary, our data suggest that PB1-F2 expression deeply affect the immune response in chickens in a way that may attenuate pathogenicity at low infection dose, a feature differing from what was previously observed in mammal species.

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“…positions 12, 25, 26, 38 and 58) [ 15 ]. Likewise, extended forms (up to 106 aa) have been reported [ 16 ]. The expression pattern of PB1-F2 is host-dependent.…”

Section: Introductionmentioning

confidence: 99%

The role of PB1-F2 in adaptation of high pathogenicity avian influenza virus H7N7 in chickens

Hohensee,

Scheibner,

Schäfer

et al. 2024

Vet Res

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Avian influenza viruses (AIV) of the H7N7 subtype are enzootic in the wild bird reservoir in Europe, cause infections in poultry, and have sporadically infected humans. The non-structural protein PB1-F2 is encoded in a second open frame in the polymerase segment PB1 and its sequence varies with the host of origin. While mammalian isolates predominantly carry truncated forms, avian isolates typically express full-length PB1-F2. PB1-F2 is a virulence factor of influenza viruses in mammals. It modulates the host immune response, causing immunopathology and increases pro-inflammatory responses. The role of full-length PB1-F2 in IAV pathogenesis as well as its impact on virus adaptation and virulence in poultry remains enigmatic. Here, we characterised recombinant high pathogenicity AIV (HPAIV) H7N7 expressing or lacking PB1-F2 in vitro and in vivo in chickens. In vitro, full-length PB1-F2 modulated viability of infected chicken fibroblasts by limiting apoptosis. In chickens, PB1-F2 promoted gastrointestinal tropism, as demonstrated by enhanced viral replication in the gut and increased cloacal shedding. PB1-F2’s effects on cellular immunity however were marginal. Overall, chickens infected with full-length PB1-F2 virus survived for shorter periods, indicating that PB1-F2 is also a virulence factor in bird-adapted viruses.

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PB1-F2 Finder: scanning influenza sequences for PB1-F2 encoding RNA segments

Cited by 6 publications

References 10 publications

The Evolution, Spread and Global Threat of H6Nx Avian Influenza Viruses

The Evolution, Spread and Global Threat of H6Nx Avian Influenza Viruses

PB1-F2 Attenuates Virulence of Highly Pathogenic Avian H5N1 Influenza Virus in Chickens

The role of PB1-F2 in adaptation of high pathogenicity avian influenza virus H7N7 in chickens

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