Evolution of H5-Type Avian Influenza A Virus Towards Mammalian Tropism in Egypt, 2014 to 2015

Mahmoud, Sara H.; Mostafa, Ahmed; El-Shesheny, Rabeh; Seddik, Mohamed Zakaraia; Khalafalla, G. M.; Shehata, Mahmoud; Kandeil, Ahmed; Pleschka, Stephan; Kayali, Ghazi; Webby, Richard J.; Veljković, Veljko; Ali, Mohamed A.

doi:10.3390/pathogens8040224

Cited by 3 publications

(3 citation statements)

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“…Due to the high genetic plasticity based on the error-prone polymerase activity and segmented genome nature, IAV can exhibit functionally adaptive substitutions and can undergo gene segment reassortment among distinct viruses [1,[8][9][10]. This enables these viruses to quickly adapt to new host species or selective/antiviral pressures.…”

Section: Discussionmentioning

confidence: 99%

“…Substitutions of polymerase subunits have been reported to alter the replication, pathogenicity, and host range of IAV in mammals and poultry [7][8][9][10]. Concerning the PB2 protein of avian influenza viruses (AIV), a glutamic acid replacement at position 627 with lysine (E627K) is known as an important host range determinant, which enhances efficient viral genome replication at mammalian-like temperature, transmissibility, and pathogenicity of AIV to mammals [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Differential Impact of Specific Amino Acid Residues on the Characteristics of Avian Influenza Viruses in Mammalian Systems

et al. 2022

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Avian influenza virus (AIV) H9N2 was declared to be endemic in birds of the Middle East, in particular in Egypt, with multiple cases of human infections. Despite concerns about the pandemic threat posed by H9N2 AIV, due to the fact that its receptor specificity is similar to that of human influenza viruses, its morbidity and mortality rates in humans are so far negligible. However, the acquisition of specific adaptive amino acid (aa) mutations in the viral polymerase can enhance cross-species transmission of the virus itself or of reassortants, which gained these changes. The polymerase basic protein 2 (PB2) is one of the key determinants for AIV adaptation towards mammals. Although mammalian pathogenicity-related mutations (MPMs) in PB2 genes were identified in different AIVs, the specific effect of single or multiple mutations on viral fitness has not been compared so far. Here, we studied the effect of the aa K at position 591, which was frequently reported in the PB2 of Egyptian H9N2 isolates, on the proliferation efficiency and polymerase activity of an H5N1 (clade 2.2.1.2) AIV already carrying the mammalian adaptive mutation 627K. Using reverse genetics, we generated a set of recombinant parental strains and H5N1 variants carrying the avian-like 591Q/627E or mammalian-like adaptive mutations 591K/627K (H5N1EGY, H9N2EGY, H5N1PB2-H9N2EGY, H5N1H9N2_PB2_K591Q, H5N1PB2_K627E, H5N1PB2_K627E/591K, H5N1PB2_627K/591K). Regardless of the avian-like 627E or the mammalian-adaptive 627K, both variants carrying the 591K (H5N1PB2_K627E/591K, H5N1PB2_627K/591K) and the reassortant H5N1PB2-H9N2EGY replicated to significantly higher levels in mammalian continuous MDCK and Calu-3 cell lines and primary normal human bronchial epithelial cells than the parental H5N1EGY virus (carrying solely the 627K adaptive mutation). Expectedly, the H5N1 variants carrying avian-like PB2 mutations (H5N1H9N2_PB2_K591Q, H5N1PB2_K627E) replicated to significantly lower levels than the parental H5N1EGY virus in the predefined primary and continuous mammalian cell line systems. Consistently, the activity of H5N1 subtype AIV polymerase complexes comprising PB2 segments with singular 591K or combined with 627K was significantly enhanced when compared to parental H5N1EGY and H9N2EGY. This study emphasizes the significant impact of 591K containing PB2 segments in the background of H5N1 polymerase on viral fitness in addition to the well-known MPM 627K in vitro.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential Impact of Specific Amino Acid Residues on the Characteristics of Avian Influenza Viruses in Mammalian Systems

et al. 2022

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“…On a larger scale, it is through the process of reassortment that novel pandemic viruses are generated (Gething et al, 1980; Smith et al, 2009). Within the avian reservoir, there is a key focus on HA subtypes that cause significant morbidity and mortality in food production birds (eg H5, H7) or have zoonotic potential (eg H5, H7, H9) (Chang et al, 2020; Chang et al, 2018; Cui et al, 2020; Mahmoud et al, 2019). We generally have a limited understanding of the evolution of LPAIV in the wild bird reservoir (Chen & Holmes, 2006, 2010; Dugan et al, 2008; Wille et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Evolutionary features of a prolific subtype of avian influenza A virus in European waterfowl

Wille

Tolf

Latorre‐Margalef

et al. 2021

Preprint

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Avian influenza A virus (AIV) is ubiquitous in waterfowl, and detected annually at high prevalence in waterfowl during the Northern Hemipshere autumn. Some AIV subtypes are globally common in waterfowl, such as H3N8, H4N6, and H6N2, and are detected in the same populations at high frequency, annually. In order to investigate genetic features associated to the long-term maintenance of common subtypes in migratory ducks, we sequenced 248 H4 viruses isolated across 8 years (2002-2009) from Mallards (Anas platyrhynchos) sampled in southeast Sweden. Phylogenetic analyses showed that both H4 and N6 sequences fell into in three distinct lineages, structured by year of isolation. Specifically, across the eight years of the study, we observed lineage replacement, whereby a different HA lineage circulated in the population each year. Analysis of deduced amino acid sequences of the HA lineages illustrated key differences in regions of the globular head of hemagglutinin that overlap with established antigentic sites in homologous hemagglutinin H3, suggesting the possibility of antigenic differences among these HA lineages. Beyond HA, lineage replacement was common to all segments, such that novel genome constellations were detected across years. A dominant genome constellation would rapidly amplify in the duck population, followed by unlinking of gene segments as a result of reassortment within 2-3 weeks following introduction. These data help reveal the evolutionary dynamics exhibited by AIV on both annual and decadal scales in an important reservoir host.

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Evolutionary features of a prolific subtype of avian influenza A virus in European waterfowl

et al. 2022

View full text Add to dashboard Cite

Avian influenza A virus (AIV) is ubiquitous in waterfowl and is detected annually at high prevalence in waterfowl during the Northern Hemisphere autumn. Some AIV subtypes are globally common in waterfowl, such as H3N8, H4N6, and H6N2, and are detected in the same populations at a high frequency, annually. In order to investigate genetic features associated to the long-term maintenance of common subtypes in migratory ducks, we sequenced 248 H4 viruses isolated across 8 years (2002–9) from mallards (Anas platyrhynchos) sampled in southeast Sweden. Phylogenetic analyses showed that both H4 and N6 sequences fell into three distinct lineages, structured by year of isolation. Specifically, across the 8 years of the study, we observed lineage replacement, whereby a different HA lineage circulated in the population each year. Analysis of deduced amino acid sequences of the HA lineages illustrated key differences in regions of the globular head of hemagglutinin that overlap with established antigenic sites in homologous hemagglutinin H3, suggesting the possibility of antigenic differences among these HA lineages. Beyond HA, lineage replacement was common to all segments, such that novel genome constellations were detected across years. A dominant genome constellation would rapidly amplify in the duck population, followed by unlinking of gene segments as a result of reassortment within 2–3 weeks following introduction. These data help reveal the evolutionary dynamics exhibited by AIV on both annual and decadal scales in an important reservoir host.

show abstract

Evolution of H5-Type Avian Influenza A Virus Towards Mammalian Tropism in Egypt, 2014 to 2015

Cited by 3 publications

References 32 publications

Differential Impact of Specific Amino Acid Residues on the Characteristics of Avian Influenza Viruses in Mammalian Systems

Differential Impact of Specific Amino Acid Residues on the Characteristics of Avian Influenza Viruses in Mammalian Systems

Evolutionary features of a prolific subtype of avian influenza A virus in European waterfowl

Evolutionary features of a prolific subtype of avian influenza A virus in European waterfowl

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