Steele, L. E. | bioRxiv Science

bioRxiv2026

Influenza A virus infection perturbs host cell glycosylation

Glycosylation is critical for viral-host cell interactions in influenza A virus (IAV) infection, but we lack a comprehensive understanding of how IAV infection shapes the host glycoproteome and the implications of these changes. Here, we used a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to perform proteomic, glycomic, and glycoproteomic characterisation of the dynamic subcellular responses to an in vitro time course infection of human A549 cells with two IAV strains (A/X-31, H3N2; and A/Puerto Rico/8/1934, H1N1). IAV infection resulted in only modest changes to the subcellular proteome, but robust and significant changes to the host secreted and organelle glycome and glycoproteome. Infection with either virus resulted in a widespread reduction in sialic acid across the N- and O-glyco(proteo)me; increased abundance of oligomannose, paucimannose, and phosphorylated glycans; and shorter hybrid/complex glycans. Reduced sialylation was consistent with desialylation of glycans by viral neuraminidase (NA), but with specific features of the glycan and protein controlling the extent of desialylation. Desialylation was greater when glycans were fucosylated; when the sialic acid was attached via an 2,3 linkage or positioned on the 3 arm; on larger, more complex glycans; and when present on proteins that are more accessible to IAV NA. Subtle but prolonged activation of the unfolded protein response in infection led to a doubling of oligomannose N-glycosylation. Glycans were shorter in infection, implicating IAV-induced disruption of Golgi glycoprotein flux as a mechanism that reduces host glycoprotein sialylation and promotes virion release, independent of NA activity. Our data provide important insights into the host glycoproteome during influenza virus infection, furthering our understanding of how influenza NA acts upon host glycans, and how cell stresses in infection perturb key mediators of protein stability and function, cell signalling and immunity.

biochemistry↗

bioRxiv2022

The swan genome and transcriptome: its not all black and white

The Australian black swan (Cygnus atratus) is an iconic species with contrasting plumage to that of the closely related Northern Hemisphere white swans. The relative geographic isolation of the black swan may have resulted in a limited immune repertoire and increased susceptibility to infectious disease, notably infectious diseases from which Australia has been largely shielded. Indeed, unlike Mallard ducks and the mute swan (Cygnus olor), the black swan is extremely sensitive to severe highly pathogenic avian influenza (HPAI). Understanding this susceptibility has been impaired by the absence of any available swan genome and transcriptome information. Here, we generate the first chromosome-length annotated black and mute swan genomes annotated with transcriptome data, all using long-read based pipelines generated for vertebrate species. We used these genomes and transcriptomes, to show that unlike other wild waterfowl, black swans lack an expanded immune gene repertoire, lack a key viral pattern-recognition receptor in endothelial cells and mount a poorly controlled inflammatory response to HPAI. We also implicate genetic differences in SLC45A2 in the iconic plumage of the Australian black swan. Together, these data suggest that the immune system of the black swan is such that should any avian viral infection become established in its native habitat the survival of the black swan would be in significant peril.

genomics↗