Emergence and epidemic occurrence of enterovirus 68 respiratory infections in The Netherlands in 2010

Meijer, Adam; Sanden, Sabine van der; Snijders, Bianca E.P.; Jaramillo-Gutierrez, Giovanna; Bont, Louis; Ent, Cornelis K. van der; Overduin, Pieter; Jenny, Shireen L.; Jusic, Edin; Avoort, H. G. A. M. Van Der; Smith, Gavin J. D.; Donker, G.A.; Koopmans, Marion

doi:10.1016/j.virol.2011.11.021

Cited by 159 publications

(262 citation statements)

References 38 publications

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“…EV-D68 was first isolated from children with respiratory infections in California in 1962 (3). It was long considered a rare pathogen, but the frequency of detecting EV-D68 during outbreaks of respiratory disease has increased (4,5) and over the past decades, three clades of EV-D68 (A, B, and C) have emerged and spread worldwide (6,7). EV-D68 infections mostly cause mild respiratory disease but can also result in severe bronchiolitis or pneumonia, especially among children (4,5).…”

mentioning

confidence: 99%

“…It was long considered a rare pathogen, but the frequency of detecting EV-D68 during outbreaks of respiratory disease has increased (4,5) and over the past decades, three clades of EV-D68 (A, B, and C) have emerged and spread worldwide (6,7). EV-D68 infections mostly cause mild respiratory disease but can also result in severe bronchiolitis or pneumonia, especially among children (4,5). In 2014, a nationwide EV-D68 outbreak in the United States was associated with severe respiratory disease and a cluster of acute flaccid myelitis and cranial nerve dysfunction in children, implicating EV-D68 as an emerging public health threat (8,9).…”

mentioning

confidence: 99%

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Enterovirus D68 receptor requirements unveiled by haploid genetics

Baggen

Thibaut

Staring

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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118

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Enterovirus D68 (EV-D68) is an emerging pathogen that can cause severe respiratory disease and is associated with cases of paralysis, especially among children. Heretofore, information on host factor requirements for EV-D68 infection is scarce. Haploid genetic screening is a powerful tool to reveal factors involved in the entry of pathogens. We performed a genome-wide haploid screen with the EV-D68 prototype Fermon strain to obtain a comprehensive overview of cellular factors supporting EV-D68 infection. We identified and confirmed several genes involved in sialic acid (Sia) biosynthesis, transport, and conjugation to be essential for infection. Moreover, by using knockout cell lines and gene reconstitution, we showed that both α2,6- and α2,3-linked Sia can be used as functional cellular EV-D68 receptors. Importantly, the screen did not reveal a specific protein receptor, suggesting that EV-D68 can use multiple redundant sialylated receptors. Upon testing recent clinical strains, we identified strains that showed a similar Sia dependency, whereas others could infect cells lacking surface Sia, indicating they can use an alternative, nonsialylated receptor. Nevertheless, these Sia-independent strains were still able to bind Sia on human erythrocytes, raising the possibility that these viruses can use multiple receptors. Sequence comparison of Sia-dependent and Sia-independent EV-D68 strains showed that many changes occurred near the canyon that might allow alternative receptor binding. Collectively, our findings provide insights into the identity of the EV-D68 receptor and suggest the possible existence of Sia-independent viruses, which are essential for understanding tropism and disease.

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mentioning

confidence: 99%

mentioning

confidence: 99%

Enterovirus D68 receptor requirements unveiled by haploid genetics

Baggen

Thibaut

Staring

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

118

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“…According to our previous reports, most of the EV68 strains detected in the Philippines belonged to lineage 2, and a few of them belonged to lineage 3 (4,10). The VP1 sequences detected in the Philippines and other countries demonstrated that the amino acid sequence patterns in BC and DE loops were correlated with the categorization of EV68 into the 3 lineages (6,8,10). Generally, loop structures, including BC and DE loops, are located on the viral surface and associated with antigenic epitopes of enteroviruses (11,12).…”

Section: H Uman Enterovirus 68 (Ev68) (Species Human Enterovirus D;mentioning

confidence: 76%

“…In an enterovirus surveillance conducted in the United States from 1970 to 2005, only a total of 26 strains were reported over 35 years (2). However, the number of reported EV68 cases increased dramatically in the late 2000s, in different parts of the world (3)(4)(5)(6)(7)(8). The underlying molecular mechanism for this sudden increase of EV68 detections in recent years is still unknown.…”

Section: H Uman Enterovirus 68 (Ev68) (Species Human Enterovirus D;mentioning

confidence: 99%

“…On the basis of nucleotide sequences of the capsid coding region VP1, the EV68 strains detected in recent years were categorized into three genetic groups, lineages 1, 2, and 3 (6,9). According to our previous reports, most of the EV68 strains detected in the Philippines belonged to lineage 2, and a few of them belonged to lineage 3 (4,10).…”

Section: H Uman Enterovirus 68 (Ev68) (Species Human Enterovirus D;mentioning

confidence: 99%

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Antigenic and Receptor Binding Properties of Enterovirus 68

Imamura

Okamoto

Nakakita

et al. 2014

J Virol

113

127

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Increased detection of enterovirus 68 (EV68) among patients with acute respiratory infections has been reported from different parts of the world in the late 2000s since its first detection in pediatric patients with lower-respiratory-tract infections in 1962. However, the underlying molecular mechanisms for this trend are still unknown. We therefore aimed to study the antigenicity and receptor binding properties of EV68 detected in recent years in comparison to the prototype strain of EV68, the Fermon strain. We first performed neutralization (NT) and hemagglutination inhibition (HI) tests using antisera generated for EV68 strains detected in recent years. We found that the Fermon strain had lower HI and NT titers than recently detected EV68 strains. The HI and NT titers were also significantly different between strains of different genetic lineages among recently detected EV68 strains. We further studied receptor binding specificities of EV68 strains for sialyloligosaccharides using glycan array analysis. In glycan array analysis, all tested EV68 strains showed affinity for ␣2-6-linked sialic acids (␣2-6 SAs) compared to ␣2-3 SAs. Our study demonstrates that emergence of strains with different antigenicity is the possible reason for the increased detection of EV68 in recent years. Additionally, we found that EV68 preferably binds to ␣2-6 SAs, which suggests that EV68 might have affinity for the upper respiratory tract. IMPORTANCE Numbers of cases of enterovirus 68 (EV68) infection in different parts of the world increased significantly in the late 2000s.We studied the antigenicity and receptor binding properties of recently detected EV68 strains in comparison to the prototype strain of EV68, Fermon. The hemagglutination inhibition (HI) and neutralization (NT) titers were significantly different between strains of different genetic lineages among recently detected EV68 strains. We further studied receptor binding specificities of EV68 strains for sialyloligosaccharides using glycan array analysis, which showed affinity for ␣2-6-linked sialic acids (␣2-6 SAs) compared to ␣2-3 SAs. Our study suggested that the emergence of strains with different antigenicities was the possible reason for the increased detections of EV68 in recent years. Additionally, we revealed that EV68 preferably binds to ␣2-6 SAs. This is the first report describing the properties of EV68 receptor binding to the specific types of sialic acids.

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Phylogenetic characterization of enterovirus 68 strains in patients with respiratory syndromes in Italy

et al. 2013

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Enterovirus 68 (EV-D68) was associated with mild to severe respiratory infections. In the last 4 years, circulation of different EV-D68 strains has been documented worldwide. In this study, the phylogenetic characterization of nine EV-D68 strains identified in patients in the 2010-2012 period and 12 additional EV-D68 Italian strains previously identified in 2008 in Italy was described. From January 2010 to December 2012, a total of 889 respiratory specimens from 588 patients stayed or visited at the Fondazione IRCCS Policlinico San Matteo were positive for HRV or HEV. Extracted nucleic acids were amplified by one-step RT-PCR with primer specific for VP1 region of EV-D68 and purified positive PCR products were directly sequenced. Overall, 9/3736 (0.24%) patients were EV-D68 positive. Of these, 7/9 (77.8%) were pediatric and two (22.2%) were adults. Five out of seven (71.4%) pediatric patients had lower respiratory tract infection with oxygen saturation <94%. Four cases were detected from August through October 2010, while five other cases from September through December 2012. The Italian EV-D68 strains in 2008 belonged to clade A (n = 5) and clade C (n = 7). In 2010 all the Italian strains belonged to clade A (n = 4) and in 2012, four Italian strains belonged to clade B and one to clade A. In conclusion, we provide additional evidence supporting a role of EV-D68 in severe respiratory infection in pediatric patients. In addition, all the three EV-D68 clades circulating worldwide were identified in Italy in a 5-year period of time.

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Emergence and epidemic occurrence of enterovirus 68 respiratory infections in The Netherlands in 2010

Cited by 159 publications

References 38 publications

Enterovirus D68 receptor requirements unveiled by haploid genetics

Enterovirus D68 receptor requirements unveiled by haploid genetics

Antigenic and Receptor Binding Properties of Enterovirus 68

Phylogenetic characterization of enterovirus 68 strains in patients with respiratory syndromes in Italy

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