Elucidation of virulence determinants of highly pathogenic non-H5, non-H7 avian influenza viruses
Virology
Final Report Abstract
The project successfully advanced our understanding of the genetic mechanisms behind the shift from low pathogenicity to high pathogenicity avian influenza viruses (AIVs) and adaptation to mammals. One major finding was the identification of phenotypic and genotypic properties essential for the emergence of high pathogenicity AIVs from low pathogenic ancestors. Reassortment of H4N2 and H4N6 with H5N1 segments increased virulence, demonstrating that non-H5/H7 subtypes can evolve into highly pathogenic strains. Critical mutations in segments such as NP, NA, and NS were linked to enhanced virulence and transmissibility, benefiting key biological traits for virus replication, including receptor binding-destruction balance, immune suppression, and polymerase activity. Additionally, experimental passage of H4N2 in fowl eggs led to a highly pathogenic phenotype, highlighting the role of intensive replication in chickens and the selection of a high-pathogenic population from the majority of low-pathogenic quasispecies. Moving forward, we will assess the biological efficiency of wild-bird origin viruses compared to HPAIV to predict the potential for circulating wild bird viruses to transform into high-virulence strains in poultry, helping mitigate the economic impact of HPAIV. Our studies also investigated the genetic determinants necessary for the adaptation of the Seal H10N7 virus in mammals, positioning seals as a critical yet underexplored intermediate species in AIV adaptation to humans. Future research will focus on host factors such as ANP32 and MX1 to better understand the role of seals in the mammalian adaptation of AIVs.
Publications
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Impact of Mutations in the Hemagglutinin of H10N7 Viruses Isolated from Seals on Virus Replication in Avian and Human Cells. Viruses, 10(2), 83.
Dittrich, Anne; Scheibner, David; Salaheldin, Ahmed; Veits, Jutta; Gischke, Marcel; Mettenleiter, Thomas & Abdelwhab, Elsayed
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Insertion of Basic Amino Acids in the Hemagglutinin Cleavage Site of H4N2 Avian Influenza Virus (AIV)—Reduced Virus Fitness in Chickens is Restored by Reassortment with Highly Pathogenic H5N1 AIV. International Journal of Molecular Sciences, 21(7), 2353.
Gischke, Marcel; Ulrich, Reiner; I., Fatola Olanrewaju; Scheibner, David; Salaheldin, Ahmed H.; Crossley, Beate; Böttcher-Friebertshäuser, Eva; Veits, Jutta; Mettenleiter, Thomas C. & Abdelwhab, Elsayed M.
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Non-basic amino acids in the hemagglutinin proteolytic cleavage site of a European H9N2 avian influenza virus modulate virulence in turkeys. Scientific Reports, 10(1).
Blaurock, Claudia; Scheibner, David; Landmann, Maria; Vallbracht, Melina; Ulrich, Reiner; Böttcher-Friebertshäuser, Eva; Mettenleiter, Thomas C. & Abdelwhab, Elsayed M.
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Preferential Selection and Contribution of Non-Structural Protein 1 (NS1) to the Efficient Transmission of Panzootic Avian Influenza H5N8 Virus Clades 2.3.4.4A and B in Chickens and Ducks. Journal of Virology, 95(18).
Blaurock, Claudia; Breithaupt, Angele; Scheibner, David; Bagato, Ola; Karger, Axel; Mettenleiter, Thomas C. & Abdelwhab, Elsayed M.
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The C-terminus of non-structural protein 1 (NS1) in H5N8 clade 2.3.4.4 avian influenza virus affects virus fitness in human cells and virulence in mice. Emerging Microbes & Infections, 10(1), 1760-1776.
Blaurock, Claudia; Blohm, Ulrike; Luttermann, Christine; Holzerland, Julia; Scheibner, David; Schäfer, Alexander; Groseth, Allison; Mettenleiter, Thomas C. & Abdelwhab, Elsayed M.
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The role of glycosylation in the N-terminus of the hemagglutinin of a unique H4N2 with a natural polybasic cleavage site in virus fitness in vitro and in vivo. Virulence, 12(1), 666-678.
Gischke, Marcel; Bagato, Ola; Breithaupt, Angele; Scheibner, David; Blaurock, Claudia; Vallbracht, Melina; Karger, Axel; Crossley, Beate; Veits, Jutta; Böttcher-Friebertshäuser, Eva; Mettenleiter, Thomas C. & Abdelwhab, Elsayed M.
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Genetic Determinants for Virulence and Transmission of the Panzootic Avian Influenza Virus H5N8 Clade 2.3.4.4 in Pekin Ducks. Journal of Virology, 96(13).
Scheibner, David; Breithaupt, Angele; Luttermann, Christine; Blaurock, Claudia; Mettenleiter, Thomas C. & Abdelwhab, Elsayed M.
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Phenotypic effects of mutations observed in the neuraminidase of human origin H5N1 influenza A viruses. PLOS Pathogens, 19(2), e1011135.
Scheibner, David; Salaheldin, Ahmed H.; Bagato, Ola; Zaeck, Luca M.; Mostafa, Ahmed; Blohm, Ulrike; Müller, Christin; Eweas, Ahmed F.; Franzke, Kati; Karger, Axel; Schäfer, Alexander; Gischke, Marcel; Hoffmann, Donata; Lerolle, Solène; Li, Xuguang; Abd, El-Hamid Hatem S.; Veits, Jutta; Breithaupt, Angele; Boons, Geert-Jan ... & Abdelwhab, Elsayed M.
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Complex N -glycans are important for interspecies transmission of H7 influenza A viruses. Journal of Virology, 98(4).
Spruit, Cindy M.; Palme, Diana I.; Li, Tiehai; Ríos, Carrasco María; Gabarroca, García Alba; Sweet, Igor R.; Kuryshko, Maryna; Maliepaard, Joshua C. L.; Reiding, Karli R.; Scheibner, David; Boons, Geert-Jan; Abdelwhab, Elsayed M. & de, Vries Robert P.
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In turkeys, unlike chickens, the non-structural NS1 protein does not play a significant role in the replication and tissue tropism of the H7N1 avian influenza virus. Virulence, 15(1).
Kuryshko, Maryna; Landmann, Maria; Luttermann, Christine; Ulrich, Reiner & Abdelwhab, Elsayed M.
