Biology subjects

Palme, D. I.

Publications and source records attributed to Palme, D. I..

2 recordsLinked to original sources

bioRxiv2025

Different genetic determinants for high virulence, transmission and replication of high pathogenicity H7N7 avian influenza virus in turkeys and chickens

High pathogenicity (HP) avian influenza viruses (AIV) generally evolve from low pathogenicity (LP) precursors after transmission from wild birds to chickens (Gallus gallus domesticus) and turkeys (Meleagris gallopavo), causing severe economic losses worldwide. Turkeys are more susceptible to AIV infection than chickens and are considered potential bridging hosts that facilitate the emergence of HPAIV. Beyond the polybasic cleavage site (pCS) in hemagglutinin (HA), little is known about other virulence determinants of HPAIV in these species. In 2015, HPAIV H7N7 and its LP ancestor were isolated from the same chicken farm, which differed by 16 nonsynonymous mutations across all eight gene segments, in addition to the pCS. Here we identify the genetic determinants, including the pCS, that contributed to the HPAIV H7N7 virulence, transmission, replication, and tissue distribution in chickens and turkeys. Notably, the non-structural (NS1) or matrix (M) proteins encoding segments in turkeys, or NS segment in chickens, rendered viruses as virulent and transmissible as the original HPAIV. Endotheliotropism, observed exclusively in chickens, was driven by the pCS and, to a lesser extent, the neuraminidase (NA). In vitro, the M2-V68L mutation influenced NS1 expression and virus morphology in chicken and turkey cells. Additionally, HPAIV NS1 enhanced polymerase activity and effectively suppressed interferon induction, a process further modulated by M2-V68L. These findings underscore the critical role of turkeys as a "hub" in the evolution of HPAIV from LP precursors, offering crucial insights into the genotypic and phenotypic factors that facilitate viral adaptation in different poultry species. ImportanceHigh pathogenicity avian influenza viruses (HPAIV) cause severe economic losses for the poultry industry worldwide. HPAIV generally evolve from low pathogenicity (LP) ancestors in galliform birds, with turkeys being more susceptible to severe disease and death than chickens. The mechanisms underlying HPAIV emergence in these species remain unclear. This study reveals two distinct evolutionary pathways for HPAIV. In turkeys, both the polybasic hemagglutinin cleavage site (pCS) and mutations in the NS or M segments contributed to high virulence and transmission. In chickens, only the NS segment was critical, in addition to the pCS. These segments increased virus replication in both chicken and turkey cells. However, unlike chicken cells, the M and NS segments did not play a role in blocking the innate immune response. Understanding these species-specific mechanisms highlights the role of turkeys as a bridging host and provides insights into the molecular evolution of HPAIV from LP precursors.

microbiology↗

bioRxiv2023

H7 influenza A viruses bind sialyl-LewisX, a potential intermediate receptor between species

Influenza A viruses (IAVs) can overcome species barriers by adaptation of the receptor binding site of the hemagglutinin (HA). To initiate infection, HAs bind to glycan receptors with terminal sialic acids, which are either N-acetylneuraminic acid (NeuAc) or N-glycolylneuraminic acid (NeuGc), the latter is mainly found in horses and pigs but not in birds and humans. We investigated the influence of previously identified equine NeuGc-adapting mutations (S128T, I130V, A135E, T189A, and K193R) in avian H7 IAVs in vitro and in vivo. We observed that these mutations negatively affected viral replication in chicken cells, but not in duck cells, and positively affected replication in horse cells. In vivo, the mutations reduced virus virulence and mortality in chickens. Ducks excreted high viral loads for a longer time than chickens, although they appeared clinically healthy. To elucidate why chickens and ducks were infected by these viruses despite the absence of NeuGc, we re-evaluated the receptor binding of H7 HAs using glycan microarray and flow cytometry studies. This revealed that mutated avian H7 HAs also bound to 2,3-linked NeuAc and sialyl-LewisX, which have an additional fucose moiety in their terminal epitope, explaining why infection of ducks and chickens was possible. Interestingly, the 2,3-linked NeuAc and sialyl-LewisX epitopes were only bound when presented on tri-antennary N-glycans, emphasizing the importance of investigating the fine receptor specificities of IAVs. In conclusion, the binding of NeuGc-adapted H7 IAV to sialyl-LewisX enables viral replication and shedding by chickens and ducks, potentially facilitating interspecies transmission of equine-adapted H7 IAVs. (249 words) ImportanceInfluenza A viruses cause millions of deaths and illness in birds and mammals each year. The viral surface protein hemagglutinin initiates infection by binding to host cell terminal sialic acids. Hemagglutinin adaptations affect the binding affinity to these sialic acids and therefore the potential host species targeted. While avian and human IAVs tend to bind N-acetylneuraminic acid (a form of sialic acid), equine H7 viruses prefer binding to N-glycolylneuraminic acid (NeuGc). To better understand the function of NeuGc-specific adaptations in hemagglutinin and to elucidate interspecies transmission potential NeuGc-adapted viruses, we evaluated the effects of NeuGc-specific mutations in avian H7 viruses in chickens and ducks, important economic hosts and reservoir birds, respectively. We also examined the impact on viral replication and found a binding affinity to sialyl-LewisX, another terminal epitope. These findings are important as they contribute to the understanding of the role of sialyl-LewisX in avian influenza infection. (148 words)

molecular biology↗