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Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance.

Abstract It is well known that large genomic variations can greatly impact the phenotype of an organism. Structural Variants (SVs) encompass any genomic variation larger than 30 base pairs, and include changes caused by deletions, inversions, duplications, transversions, and other genome modifications. Due to their size and complex nature, until recently, it has been difficult to truly capture these variations. Recent advances in sequencing technology and computational analyses now permit more extensive studies of SVs in plant genomes. In tomato, advances in sequencing technology have allowed researchers to sequence hundreds of genomes from tomatoes, and tomato relatives. These studies have identified SVs related to fruit size and flavor, as well as plant disease response, resistance/susceptibility, and the ability of plants to detect pathogens (immunity). In this review, we discuss the implications for genomic structural variation in plants with a focus on its role in tomato immunity. We also discuss how advances in sequencing technology have led to new discoveries of SVs in more complex genomes, the current evidence for the role of SVs in biotic and abiotic stress responses, and the outlook for genetic modification of SVs to advance plant breeding objectives.