Glycan remodeled erythrocytes facilitate antigenic characterization of recent A/H3N2 influenza viruses

Broszeit, Frederik; Beek, Rosanne J. van; Unione, Luca; Bestebroer, Theo M.; Chapla, Digantkumar; Yang, Jeong‐Yeh; Moremen, Kelley W.; Herfst, Sander; Fouchier, Ron A. M.; Vries, Robert P. de; Boons, Geert‐Jan

doi:10.1101/2020.12.18.423398

Cited by 11 publications

(19 citation statements)

References 39 publications

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“…For H3N2 viruses, the amino acid substitutions at positions 190, 226, and 194 of HA were associated with the loss of the ability for the A(H3N2) viruses to agglutinate chicken erythrocytes [234,[236][237][238][239]. Since the 2004-2005 influenza season, A(H3N2) viruses acquired Asp225Asn in HA, which caused the loss of their binding abilities to turkey erythrocytes [227,230]; this may be attributed to the inability of viral binding to short oligosaccharides terminated with sialic acids (i.e., those having only one or two N-acetyl-lactosamine repeating units), which are mainly expressed by chicken or turkey erythrocytes [240]. As an extreme example, a large portion of A(H3N2) viruses, especially clade 3C.2a viruses, have lost the capacity to agglutinate chicken, turkey, and guinea pig erythrocytes [229,241]; thus, they cannot be antigenically characterized by HI assays.…”

Section: Hi Assaymentioning

confidence: 99%

Antigenic characterization of influenza and SARS-CoV-2 viruses

2021

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Antigenic characterization of emerging and re-emerging viruses is necessary for the prevention of and response to outbreaks, evaluation of infection mechanisms, understanding of virus evolution, and selection of strains for vaccine development. Primary analytic methods, including enzyme-linked immunosorbent/lectin assays, hemagglutination inhibition, neuraminidase inhibition, micro-neutralization assays, and antigenic cartography, have been widely used in the field of influenza research. These techniques have been improved upon over time for increased analytical capacity, and some have been mobilized for the rapid characterization of the SARS-CoV-2 virus as well as its variants, facilitating the development of highly effective vaccines within 1 year of the initially reported outbreak. While great strides have been made for evaluating the antigenic properties of these viruses, multiple challenges prevent efficient vaccine strain selection and accurate assessment. For influenza, these barriers include the requirement for a large virus quantity to perform the assays, more than what can typically be provided by the clinical samples alone, cell- or egg-adapted mutations that can cause antigenic mismatch between the vaccine strain and circulating viruses, and up to a 6-month duration of vaccine development after vaccine strain selection, which allows viruses to continue evolving with potential for antigenic drift and, thus, antigenic mismatch between the vaccine strain and the emerging epidemic strain. SARS-CoV-2 characterization has faced similar challenges with the additional barrier of the need for facilities with high biosafety levels due to its infectious nature. In this study, we review the primary analytic methods used for antigenic characterization of influenza and SARS-CoV-2 and discuss the barriers of these methods and current developments for addressing these challenges.

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Section: Hi Assaymentioning

confidence: 99%

Antigenic characterization of influenza and SARS-CoV-2 viruses

2021

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“…However, it remains unknown if a specific type of glycoconjugate serves as the primary receptor or if multiple glycoconjugates are capable of facilitating IAV entry. Much of our understanding of the utilization of glycoconjugate types by various IAV strains has been inferred from in vitro virion or purified HA binding assays on glycan array slides (Byrd-Leotis et al, 2019b;Byrd-Leotis et al, 2014;Connor et al, 1994;Jia et al, 2020;Rogers and Paulson, 1983;Stevens et al, 2006) (Broszeit et al, 2021;Byrd-Leotis et al, 2019a;Peng et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…These studies suggest that human IAV strains preferentially bound to long branched sialoglycans with poly-lactosamine (polyLN) repeats that had an 'umbrella-like' topology, whereas avian IAV strains preferentially bound to short sialoglycans with a single lactosamine that had a 'cone-like' topology, indicating that glycan topology can also determine host range (Chandrasekaran et al, 2008). In agreement, circulating human H3N2 viruses have evolved to utilize extended branched polyLN glycans (N-glycans), while the parental pandemic H3N2 strain preferentially bound to short sialyl-LN glycans (Broszeit et al, 2021;Byrd-Leotis et al, 2019a;Peng et al, 2017). In array slides, glycans are immobilized in non-natural configurations at a high density with uniformity and hence, the conclusions can be biased on the repertoire of glycans presented (Raman et al, 2014;Shi et al, 2014).…”

Section: Introductionmentioning

confidence: 93%

Avian and Human Influenza Viruses Exhibit Distinct Glycoconjugate Receptor Specificities in Human Lung Cells

Liang

Huang

Han

et al. 2022

Preprint

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IAV utilize sialic acid (Sia) containing cell surface glycoconjugates for host cell infection, and IAV strains from different host species show preferences for structurally distinct Sia at the termini of glycoconjugates. Various types of cell surface glycoconjugates (N-glycans, O-glycans, glycolipids) display significant diversity in both structure and carbohydrate composition. To define the types of glycoconjugates that facilitate IAV infection, we utilized the CRISPR/Cas9 technique to truncate different types of glycoconjugates, either individually or in combination, by targeting glycosyltransferases essential to glycan biosynthesis in a human lung epithelial cell line. Our studies show that both human and avian IAV strains do not display strict preferences for a specific type of glycoconjugate. Interestingly, truncation of all three types of glycoconjugates significantly decreased the replication of human IAV strains, yet did not impact the replication of avian IAV strains. Taken together, our studies demonstrate that avian IAV strains utilize a broader repertoire of glycoconjugates for host cell infection as compared to human IAV strains.Author SummaryIt is well known that influenza A viruses (IAV) initiate host cell infection by binding to sialic acid, a sugar molecule present at the ends of various sugar chains called glycoconjugates. These glycoconjugates can vary in chain length, structure, and composition. However, it remains unknown if IAV strains preferentially bind to sialic acid on specific glycoconjugates for host cell infection. Here, we utilized CRISPR gene editing to abolish sialic acid on different glycoconjugate types in human lung cells, and evaluated human versus avian IAV infections. Our studies show that both human and avian IAV strains can infect human lung cells by utilizing any of the three major sialic acid-containing glycoconjugate types, specifically N-glycans, O-glycans, and glycolipids. Interestingly, simultaneous elimination of sialic acid on all three glycoconjugate types in human lung cells dramatically decreased human IAV infection, yet had little effect on avian IAV infection. Our studies indicate that avian IAV strains can utilize a wide variety of glycoconjugates for infection, whereas human IAV strains display restrictions in glycoconjugate type usage. These novel studies show distinct differences in host glycoconjugate preferences between human and avian IAV strains.

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“…The haemagglutination inhibition patterns were then read out and used for the calculation of antibody titres. Due to the known inefficient agglutination of tRBCs by recent A/H3N2 viruses, we used glycan remodelled turkey red blood cells expressing appropriate receptors for recent A/H3N2 viruses 26 for the implementation of the assay for the A/H3N2 virus stock.…”

Section: Methodsmentioning

confidence: 99%

Potential impacts of prolonged absence of influenza virus circulation on subsequent epidemics

Garza

Jong

Gibson

et al. 2022

Preprint

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Seasonal influenza viruses typically cause annual epidemics worldwide infecting 5-15% of the human population. However, during the first two years of the COVID-19 pandemic, seasonal influenza virus circulation was unprecedentedly low with very few reported infections. The lack of immune stimulation to influenza viruses during this time, combined with waning antibody titres to previous influenza virus infections, could lead to increased susceptibility to influenza in the coming seasons and to larger and more severe epidemics when infection prevention measures against COVID-19 are relaxed. Here, based on serum samples from 165 adults collected longitudinally before and during the pandemic, we show that the waning of antibody titres against seasonal influenza viruses during the first two years of the pandemic is likely to be negligible. Using historical influenza virus epidemiological data from 2003-2019, we also show that low country-level prevalence of each influenza subtype over one or more years has only small impacts on subsequent epidemic size. These results suggest that the risks posed by seasonal influenza viruses remained largely unchanged during the first two years of the COVID-19 pandemic and that the sizes of future seasonal influenza virus epidemics will likely be similar to those observed before the pandemic.

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Glycan remodeled erythrocytes facilitate antigenic characterization of recent A/H3N2 influenza viruses

Cited by 11 publications

References 39 publications

Antigenic characterization of influenza and SARS-CoV-2 viruses

Antigenic characterization of influenza and SARS-CoV-2 viruses

Avian and Human Influenza Viruses Exhibit Distinct Glycoconjugate Receptor Specificities in Human Lung Cells

Potential impacts of prolonged absence of influenza virus circulation on subsequent epidemics

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