Differential Disease Severity and Whole Genome Sequence Analysis for Human Influenza A/H1N1pdm Virus in 2015-2016 Influenza Season

Liu, Hsuan; Gong, Yu-Nong; Shaw‐Saliba, Kathryn; Mehoke, Thomas; Evans, Jared D.; Liu, Zhen-Ying; Lewis, Mitra; Sauer, Lauren; Thielen, Peter; Rothman, Richard E.; Chen, Kuan-Fu; Pekosz, Andrew

doi:10.1101/2020.02.20.957068

Cited by 3 publications

(9 citation statements)

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“…We found a wide diversity of A(H1N1)pdm09 strain variants in concurrent circulation, mainly within antigenic drift clades 6B.1 and 6B.2. Clade 6B.1 and 6B.2 A(H1N1)pdm09 viruses became dominant in 2015/16 across the world, including Europe, and were associated with increased hospital admissions and more severe disease in clinical cases [8,10,19,28,38]. The 6B.1 clade dominated human cases in the 2015/16 influenza season in Europe, a pattern we observed by the sequence analysis of Ukrainian A(H1N1)pdm09 strains (Figure 2).…”

Section: Discussionmentioning

confidence: 54%

“…To understand the genetic basis for the severity of ILI and SARI in Ukraine, we conducted molecular genetics and phylogenetics analyses of A(H1N1)pdm09 influenza viruses from SARI cases that circulated in Ukraine during the 2015/16 epidemic season. We found that most of the A(H1N1)pdm09 influenza viruses circulating in Ukraine were of the H1 6B.1 lineage that became predominant worldwide and was associated with antigenic escape from immunity [7][8][9][10]. Our study also revealed the emergence of new genotypic variants in Ukraine, containing unique amino-acid substitutions in HA, NS1, and other viral genes.…”

Section: Introductionmentioning

confidence: 54%

“…The 6B.1 clade dominated human cases in the 2015/16 influenza season in Europe, a pattern we observed by the sequence analysis of Ukrainian A(H1N1)pdm09 strains (Figure 2). In Taiwan, influenza cases in seasons 2013/14 and 2015/16, dominated by 6B, 6B.1, and 6B.2 clades, were at a significantly higher risk of pneumonia (1.8-fold higher risk), the need for oxygen therapy (2.6-fold), and acute respiratory distress syndrome (ARDS, 5.5-fold) [7]; clade 6B.2 infections were still at even a higher risk (3.3-fold) for pneumonia [9,10]. Epidemiological and genetic analyses suggested that clades 6B.1 and 6B.2 harbor some capacity to evade vaccine-induced immunity, mediated by an escape mutations (e.g., S162N, K163Q) in the Sa antigenic site in H1 HA that may evade neutralizing antibodies induced by vaccination [7,8,32].…”

Section: Discussionmentioning

confidence: 99%

“…Antigenic sites consist of the most variable amino acids in the HA molecule of the seasonal human H1N1 viruses that were subjected to intense antibody-mediated immune pressure, the basis for frequent updates to the composition of seasonal influenza vaccines [52]. S84N and the S162N substitution in the Sa antigenic site were observed in all isolates of the 6B.1 genetic group, adding potential N-linked glycosylation sites and an evolutionary advantage to 6B.1 strains that became predominant worldwide beginning in 2015 [10,32]. An additional mutation (S83P) in antigenic site Cb, a receptor-binding residue and target for the neutralizing antibody, was found in 11 of the Ukrainian 6B.1 strains, suggesting continual selective pressure on HA in an immunologically experienced population [32][33][34]52].…”

Section: Discussionmentioning

confidence: 99%

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Genotypic Variants of Pandemic H1N1 Influenza A Viruses Isolated from Severe Acute Respiratory Infections in Ukraine during the 2015/16 Influenza Season

Zolotarova

Фесенко

Holubka

et al. 2021

Viruses

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Human type A influenza viruses A(H1N1)pdm09 have caused seasonal epidemics of influenza since the 2009–2010 pandemic. A(H1N1)pdm09 viruses had a leading role in the severe epidemic season of 2015/16 in the Northern Hemisphere and caused a high incidence of acute respiratory infection (ARI) in Ukraine. Serious complications of influenza-associated severe ARI (SARI) were observed in the very young and individuals at increased risk, and 391 fatal cases occurred in the 2015/16 epidemic season. We analyzed the genetic changes in the genomes of A(H1N1)pdm09 influenza viruses isolated from SARI cases in Ukraine during the 2015/16 season. The viral hemagglutinin (HA) fell in H1 group 6B.1 for all but four isolates, with known mutations affecting glycosylation, the Sa antigenic site (S162N in all 6B.1 isolates), or virulence (D222G/N in two isolates). Other mutations occurred in antigenic site Ca (A141P and S236P), and a subgroup of four strains were in group 6B.2, with potential alterations to antigenicity in A(H1N1)pdm09 viruses circulating in 2015/16 in Ukraine. A cluster of Ukrainian isolates exhibited novel D2E and N48S mutations in the RNA binding domain, and E125D in the effector domain, of immune evasion nonstructural protein 1 (NS1). The diverse spectrum of amino-acid substitutions in HA, NS1, and other viral proteins including nucleoprotein (NP) and the polymerase complex suggested the concurrent circulation of multiple lineages of A(H1N1)pdm09 influenza viruses in the human population in Ukraine, a country with low vaccination coverage, complicating public health measures against influenza.

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Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genotypic Variants of Pandemic H1N1 Influenza A Viruses Isolated from Severe Acute Respiratory Infections in Ukraine during the 2015/16 Influenza Season

Zolotarova

Фесенко

Holubka

et al. 2021

Viruses

View full text Add to dashboard Cite

show abstract

“…After the novel influenza A/H1N1 virus (H1N1pdm09) emerged in 2009, it supplanted previous human H1N1 viruses to become a seasonal human H1N1 virus. 6 It is unknown how circulation of novel influenza viruses affects influenza seasonality. Therefore, to improve the current vaccination strategy, which was formulated with national 2005-2011 influenza seasonality in mind, it is useful for public health policy makers to understand important changes in influenza seasonality during the most recent decade.…”

Section: Introductionmentioning

confidence: 99%

Characterization of influenza seasonality in China, 2010–2018: Implications for seasonal influenza vaccination timing

Liao

Xue

Xie

et al. 2022

Influenza Resp Viruses

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Background Optimizing the timing of influenza vaccination based on regional temporal seasonal influenza illness patterns may make seasonal influenza vaccination more effective in China. Methods We obtained provincial weekly influenza surveillance data for 30 of 31 provinces in mainland China from the Chinese Center for Disease Control and Prevention for the years 2010–2018. Influenza epidemiological regions were constructed by clustering analysis. For each region, we calculated onset date, end date, and duration of seasonal influenza epidemics by the modified mean threshold method. To help identify initial vaccination target populations, we acquired weekly influenza surveillance data for four age groups (0–4, 5–18, 19–59, and ≥60 years) in each region and in 171 cities of wide‐ranging size. We used linear regression analyses to explore the association of epidemic onset dates by age group, city, and epidemiological region and provide evidence for initial target populations for seasonal influenza vaccination. Results We determined that northern, mid, southwestern, southeast regions of mainland China have distinct seasonal influenza epidemic patterns. We found significant regional, temporal, and spatial heterogeneity of seasonal influenza epidemics. There were significant differences by age group and city size in the interval between epidemic onset in the city or age group and regional spread (epidemic lead time), with longer epidemic lead times for 5‐ to 18‐year‐old children and larger cities. Conclusions Knowledge of influenza epidemic characteristics may help optimize local influenza vaccination timing and identify initial target groups for seasonal influenza vaccination in mainland China. Similar analyses may help inform seasonal influenza vaccination strategies in other regions and countries.

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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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Differential Disease Severity and Whole Genome Sequence Analysis for Human Influenza A/H1N1pdm Virus in 2015-2016 Influenza Season

Cited by 3 publications

References 49 publications

Genotypic Variants of Pandemic H1N1 Influenza A Viruses Isolated from Severe Acute Respiratory Infections in Ukraine during the 2015/16 Influenza Season

Genotypic Variants of Pandemic H1N1 Influenza A Viruses Isolated from Severe Acute Respiratory Infections in Ukraine during the 2015/16 Influenza Season

Characterization of influenza seasonality in China, 2010–2018: Implications for seasonal influenza vaccination timing

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

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