HA and M2 sequences alter the replication of 2013–16 H1 live attenuated influenza vaccine infection in human nasal epithelial cell cultures

Canaday, Laura M.; Resnick, Jessica D; Liu, Hsuan; Powell, Harrison; McCoy, Alyssa M.; Nguyen, Dat; Pekosz, Andrew

doi:10.1016/j.vaccine.2022.05.088

Cited by 7 publications

(13 citation statements)

References 30 publications

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“…This is especially interesting in the IAV condition in which there was no difference in the amount of infectious virus produced over time, but there was a difference in the cellular response due to temperature that was most obvious at 96 HPI. This is in contrast to other studies that have showed innate responses being proportional to infectious virus titer and thus warrants further study [ 45 , 75 ].…”

Section: Discussioncontrasting

confidence: 89%

“…Additionally, SCV2 showed significantly slower replication kinetics compared to IAV at 33 °C ( Figure 1 C) and 37 °C ( Figure 1 D). Basolateral supernatant from mock-, IAV-, or SCV2-infected hNEC cultures was collected 48 and 96 HPI, and secreted interferon, cytokines, and chemokines related to the proinflammatory response were measured by ELISA and MSD assay, as has been previously described to evaluate epithelial responses to infection [ 39 , 44 , 45 ] ( Figure 2 ). While cytokine production and release is directional in polarized epithelial cells, previous research has shown that apical versus basolateral release differs mainly in quantity, rather than type, of cytokine released [ 39 , 44 ].…”

Section: Resultsmentioning

confidence: 99%

“…Future work will investigate viral factors that contribute to temperature sensitivity. For example, in IAV infection, mutations in both the HA and M2 protein along with the replication machinery have been shown to impact temperature sensitivity in a subtype-specific manner [ 44 , 45 ]. In SCV2, the non-structural proteins have been implicated in manipulating the host response to infection, making them enticing targets in regard to temperature sensitivity [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

“…USA) according to the manufacturers’ instructions. This panel has been used previously to characterize IAV infections of epithelial cells [ 39 , 44 , 45 ]. Each sample was analyzed in duplicate.…”

Section: Methodsmentioning

confidence: 99%

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Early Transcriptional Responses of Human Nasal Epithelial Cells to Infection with Influenza A and SARS-CoV-2 Virus Differ and Are Influenced by Physiological Temperature

2023

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Influenza A (IAV) and SARS-CoV-2 (SCV2) viruses represent an ongoing threat to public health. Both viruses target the respiratory tract, which consists of a gradient of cell types, receptor expression, and temperature. Environmental temperature has been an understudied contributor to infection susceptibility and understanding its impact on host responses to infection could help uncover new insight into severe disease risk factors. As the nasal passageways are the initial site of respiratory virus infection, in this study we investigated the effect of temperature on host responses in human nasal epithelial cells (hNECs) utilizing IAV and SCV2 in vitro infection models. We demonstrate that temperature affected SCV2, but not IAV, viral replicative fitness and that SCV2-infected cultures were slower to mount an infection-induced response, likely due to suppression by the virus. Additionally, we show that that temperature not only changed the basal transcriptomic landscape of epithelial cells, but that it also impacted the response to infection. The induction of interferon and other innate immune responses was not drastically affected by temperature, suggesting that while the baseline antiviral response at different temperatures remained consistent, there may be metabolic or signaling changes that affect how well the cultures were able to adapt to new pressures, such as infection. Finally, we show that hNECs responded differently to IAV and SCV2 infection in ways that give insight into how the virus is able to manipulate the cell to allow for replication and release. Taken together, these data give new insight into the innate immune response to respiratory infections and can assist in identifying new treatment strategies for respiratory infections.

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Section: Discussioncontrasting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Early Transcriptional Responses of Human Nasal Epithelial Cells to Infection with Influenza A and SARS-CoV-2 Virus Differ and Are Influenced by Physiological Temperature

2023

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“…Growth curves were also performed on human nasal epithelial cell (hNEC) cultures, a primary cell culture model that is physiologically similar to the upper respiratory tract that seasonal influenza preferentially infect 5,[28][29][30][31][32][33] . Growth curves on hNEC cultures reflected MDCK-SIAT growth curves, with A5a.2 producing significantly reduced titers at multiple timepoints including a sustained reduction in viral replication post-peak titer (Figure 3B).…”

Section: Resultsmentioning

confidence: 99%

2019-20 H1N1 clade A5a.1 viruses have betterin vitroreplication compared with the co-circulating A5a.2 clade

Swanson

Marinho

Dziedzic

et al. 2023

Preprint

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Surveillance for emerging human influenza virus clades is important for identifying changes in viral fitness and assessing antigenic similarity to vaccine strains. While fitness and antigenic structure are both important aspects of virus success, they are distinct characteristics and do not always change in a complementary manner. The 2019-20 Northern Hemisphere influenza season saw the emergence of two H1N1 clades: A5a.1 and A5a.2. While several studies indicated that A5a.2 showed similar or even increased antigenic drift compared with A5a.1, the A5a.1 clade was still the predominant circulating clade that season. Clinical isolates of representative viruses from these clades were collected in Baltimore, Maryland during the 2019-20 season and multiple assays were performed to compare both antigenic drift and viral fitness between clades. Neutralization assays performed on serum from healthcare workers pre- and post-vaccination during the 2019-20 season show a comparable drop in neutralizing titers against both A5a.1 and A5a.2 viruses compared with the vaccine strain, indicating that A5a.1 did not have antigenic advantages over A5a.2 that would explain its predominance in this population. Plaque assays were performed to investigate fitness differences, and the A5a.2 virus produced significantly smaller plaques compared with viruses from A5a.1 or the parental A5a clade. To assess viral replication, low MOI growth curves were performed on both MDCK-SIAT and primary differentiated human nasal epithelial cell cultures. In both cell cultures, A5a.2 yielded significantly reduced viral titers at multiple timepoints post-infection compared with A5a.1 or A5a. Receptor binding was then investigated through glycan array experiments which showed a reduction in receptor binding diversity for A5a.2, with fewer glycans bound and a higher percentage of total binding attributable to the top three highest bound glycans. Together these data indicate that the A5a.2 clade had a reduction in viral fitness, including reductions in receptor binding, that may have contributed to the limited prevalence observed after emergence.

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2019–2020 H1N1 clade A5a.1 viruses have better in vitro fitness compared with the co-circulating A5a.2 clade

Swanson

Marinho

Dziedzic

et al. 2023

Sci Rep

Self Cite

View full text Add to dashboard Cite

Surveillance for emerging human influenza virus clades is important for identifying changes in viral fitness and assessing antigenic similarity to vaccine strains. While fitness and antigenic structure are both important aspects of virus success, they are distinct characteristics and do not always change in a complementary manner. The 2019–2020 Northern Hemisphere influenza season saw the emergence of two H1N1 clades: A5a.1 and A5a.2. While several studies indicated that A5a.2 showed similar or even increased antigenic drift compared with A5a.1, the A5a.1 clade was still the predominant circulating clade that season. Clinical isolates of representative viruses from these clades were collected in Baltimore, Maryland during the 2019–2020 season and multiple assays were performed to compare both antigenic drift and viral fitness between clades. Neutralization assays performed on serum from healthcare workers pre- and post-vaccination during the 2019–2020 season show a comparable drop in neutralizing titers against both A5a.1 and A5a.2 viruses compared with the vaccine strain, indicating that A5a.1 did not have antigenic advantages over A5a.2 that would explain its predominance in this population. Plaque assays were performed to investigate fitness differences, and the A5a.2 virus produced significantly smaller plaques compared with viruses from A5a.1 or the parental A5a clade. To assess viral replication, low MOI growth curves were performed on both MDCK-SIAT and primary differentiated human nasal epithelial cell cultures. In both cell cultures, A5a.2 yielded significantly reduced viral titers at multiple timepoints post-infection compared with A5a.1 or A5a. Receptor binding was then investigated through glycan array experiments which showed a reduction in receptor binding diversity for A5a.2, with fewer glycans bound and a higher percentage of total binding attributable to the top three highest bound glycans. Together these data indicate that the A5a.2 clade had a reduction in viral fitness, including reductions in receptor binding, that may have contributed to the limited prevalence observed after emergence.

show abstract

HA and M2 sequences alter the replication of 2013–16 H1 live attenuated influenza vaccine infection in human nasal epithelial cell cultures

Cited by 7 publications

References 30 publications

Early Transcriptional Responses of Human Nasal Epithelial Cells to Infection with Influenza A and SARS-CoV-2 Virus Differ and Are Influenced by Physiological Temperature

Early Transcriptional Responses of Human Nasal Epithelial Cells to Infection with Influenza A and SARS-CoV-2 Virus Differ and Are Influenced by Physiological Temperature

2019-20 H1N1 clade A5a.1 viruses have betterin vitroreplication compared with the co-circulating A5a.2 clade

2019–2020 H1N1 clade A5a.1 viruses have better in vitro fitness compared with the co-circulating A5a.2 clade

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