Search for: All records

While mammals can be infected by influenza A virus either sporadically or with well adapted lineages, aquatic birds are the natural reservoir of the pathogen. So far most of the knowledge on influenza virus dynamics was however gained on mammalian models. In this study, we infected turkeys using a low pathogenic avian influenza virus and determined the infection dynamics with a target-cell limited model. Results showed that turkeys had a different set of infection characteristics, compared with humans and ponies. The viral clearance rates were similar between turkeys and ponies but higher than that in humans. The cell death rates and cell to cell transmission rates were similar between turkeys and humans but higher than those in ponies. Overall, this study indicated the variations of within-host dynamics of influenza infection in avian, humans, and other mammalian systems. 

ABSTRACT Between 2013 and 2018, the novel A/Anhui/1/2013 (AH/13)-lineage H7N9 virus caused at least five waves of outbreaks in humans, totaling 1,567 confirmed human cases in China. Surveillance data indicated a disproportionate distribution of poultry infected with this AH/13-lineage virus, and laboratory experiments demonstrated that this virus can efficiently spread among chickens but not among Pekin ducks. The underlying mechanism of this selective transmission remains unclear. In this study, we demonstrated the absence of Neu5Gc expression in chickens across all respiratory and gastrointestinal tissues. However, Neu5Gc expression varied among different duck species and even within the tissues of the same species. The AH/13-lineage viruses exclusively bind to acetylneuraminic acid (Neu5Ac), in contrast to wild waterbird H7 viruses that bind both Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). The level of Neu5Gc expression influences H7 virus replication and facilitates adaptive mutations in these viruses. In summary, our findings highlight the critical role of Neu5Gc in affecting the host range and interspecies transmission dynamics of H7 viruses among avian species.IMPORTANCEMigratory waterfowl, gulls, and shorebirds are natural reservoirs for influenza A viruses (IAVs) that can occasionally spill over to domestic poultry, and ultimately humans. This study showed wild-type H7 IAVs from waterbirds initially bind to glycan receptors terminated with N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc). However, after enzootic transmission in chickens, the viruses exclusively bind to Neu5Ac. The absence of Neu5Gc expression in gallinaceous poultry, particularly chickens, exerts selective pressure, shaping IAV populations, and promoting the acquisition of adaptive amino acid substitutions in the hemagglutinin protein. This results in the loss of Neu5Gc binding and an increase in virus transmissibility in gallinaceous poultry, particularly chickens. Consequently, the transmission capability of these poultry-adapted H7 IAVs in wild water birds decreases. Timely intervention, such as stamping out, may help reduce virus adaptation to domestic chicken populations and lower the risk of enzootic outbreaks, including those caused by IAVs exhibiting high pathogenicity. 

Bisected N -glycans represent a unique class of protein N -glycans that play critical roles in many biological processes. Herein, we describe the systematic synthesis of these structures. A bisected N -glycan hexasaccharide was chemically assembled with two orthogonal protecting groups attached at the C2 of the branching mannose residues, followed by sequential installation of GlcNAc and LacNAc building blocks to afford two asymmetric bisecting “cores”. Subsequent enzymatic modular extension of the “cores” yielded a comprehensive library of biantennary N -glycans containing the bisecting GlcNAc and presenting 6 common glycan determinants in a combinatorial fashion. These bisected N -glycans and their non-bisected counterparts were used to construct a distinctive glycan microarray to study their recognition by a wide variety of glycan-binding proteins (GBPs), including plant lectins, animal lectins, and influenza A virus hemagglutinins. Significantly, the bisecting GlcNAc could bestow (PHA-L, rDCIR2), enhance (PHA-E), or abolish (ConA, GNL, anti-CD15s antibody, etc. ) N -glycan recognition of specific GBPs, and is tolerated by many others. In summary, synthesized compounds and the unique glycan microarray provide ideal standards and tools for glycoanalysis and functional glycomic studies. The microarray data provide new information regarding the fine details of N -glycan recognition by GBPs, and in turn improve their applications.