#Genetic Diversity of the Non-Polio #Enteroviruses Detected in Samples of Patients with Aseptic #Meningitis in the #Ural Federal District and Western #Siberia

 

Abstract

Human non-polio enteroviruses (NPEVs) cause a plethora of infections in humans, ranging from mild to severe neurological diseases including aseptic meningitis. NPEVs are the leading cause of aseptic meningitis in both children and adults worldwide. In Russia, reports of NPEV infections have surged, especially in the post-COVID era starting in 2022, with elevated infection rates into 2023. A comprehensive examination of the whole genome is crucial for understanding the evolution of NPEV genes and for predicting potential outbreaks. This study focused on identifying the circulating NPEV strains in the Ural Federal District and Western Siberia, using Sanger sequencing and next-generation sequencing (NGS) methodologies. Biological samples were collected from (n = 225) patients diagnosed with aseptic meningitis. Bioinformatics analysis targeted the nucleotide sequences of the major capsid protein (partial VP1) gene fragment, and the assembly of whole NPEV genomes. A total of 159 NPEVs were characterized, representing 70.7% of the collected samples. The main capsid variants forming the predominant genotypic profile included E30 (n = 39, 24.3%), E6 (n = 31, 19.3%), and CVA9 (n = 25, 15.6%). Using NGS, we successfully assembled 13 whole genomes for E6, E30, EV-B80, CVA9, CVB5, E11, and EV-A71 and 3 partial genomes for E6 and EV-B87. This molecular-genetic analysis provides contemporary insights into the genotypic composition, circulation patterns, and evolutionary dynamics of the dominant NPEV associated with aseptic meningitis in the Ural Federal District and Western Siberia. The laboratory-based monitoring and epidemiological surveillance for genetic changes and evolutionary studies are important for improving prevention and healthcare.

Source: 

Link: https://www.mdpi.com/1999-4915/18/1/121

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#Enterovirus D68 #Sequence #Variations and #Pathogenicity: A Review

Abstract

Enterovirus D68 (EV-D68), a neurotropic respiratory pathogen, poses a considerable clinical threat through its link to pediatric acute flaccid myelitis (AFM) and severe respiratory illness. The possibility of recurrent epidemics, evidenced since the 2014 outbreak, remains a major concern. Genomic determinants of virulence are central to this threat. Sequence variations that affect host–receptor interactions, immune evasion, and replication efficiency serve as critical modifiers of pathogenicity. This article systematically reviews the evidence for specific genomic sites that enhance EV-D68 virulence, focusing on three critical regions: the VP1 receptor-binding site, the 2Apro/TRAF3 cleavage site, and the 3Cpro immunoregulatory region. Mutations in the VP1 receptor-binding site can alter affinity for host receptors such as sialic acid, heparan sulfate, and MFSD6, thereby shaping viral entry and tissue tropism. Alterations in the 2Apro/TRAF3 cleavage site may impair proteolytic cleavage of host TRAF3, attenuating immune evasion and reducing viral pathogenicity. Variations in the 3Cpro region affect its efficiency in cleaving host proteins involved in translation and autophagy, ultimately modulating viral replication and antiviral responses. Finally, we propose that monitoring for mutations in these key virulence determinants, particularly within the surface-exposed VP1, is essential for effective outbreak preparedness.

Source: 

Link: https://www.mdpi.com/1999-4915/18/1/73

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Dynamics of endemic #virus re-emergence in #children in #USA following #COVID19 #pandemic (2022–23): a prospective, multicentre, longitudinal, immunoepidemiological surveillance study

Summary

Background

The Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) programme was established to translate knowledge gained from global immunoepidemiological surveillance into a better understanding of population-level dynamics of emerging and re-emerging infections, as well as into the discovery and development of biomedical countermeasures against potential pandemic threats. As proof of principle for this approach, we conducted a longitudinal immunoepidemiological study in children in the USA, focusing on enterovirus D68 (EV-D68) infection dynamics but also capturing surveillance of a broad array of other endemic respiratory pathogens. Serendipitously, our sampling spanned the lifting of widespread COVID-19 non-pharmaceutical interventions (NPIs) in 2022–23, following a unique period during which virus exposure markedly diminished.

Methods

This prospective, multicentre, longitudinal, immunoepidemiological surveillance study enrolled children aged 10 years or younger and weighing at least 8 kg at three US university sites. Blood specimens collected from January to June, 2022 (visit 1; pre-enterovirus season), and from January to June, 2023 (visit 3; post-enterovirus season), were tested in a multiplex assay for antibody binding to EV-D68 (prespecified primary objective) and a panel of 15 other respiratory viruses (exploratory objectives), and for neutralising activity against EV-D68, enterovirus A71, and respiratory syncytial virus (RSV; for antibody binding assay validation). Respiratory mid-turbinate swabs collected from children with symptomatic illness who participated in symptom surveys during July–December, 2022 (visit 2; enterovirus season), underwent metagenomic sequencing for pathogen detection. Serological data for EV-D68 were incorporated into epidemiological models based on case data from national surveillance to predict future transmission dynamics.

Findings

Of 488 eligible children approached, 174, with a median age of 3·4 years (IQR 1·9–6·4), were enrolled and followed up longitudinally from January, 2022, to June, 2023. Three children withdrew before study completion and 51 were lost to follow-up between visits 1 and 3. 90 paired serological samples and 73 respiratory swabs were tested. Mean antibody binding and neutralisation titres against all viruses tested increased over the study period, most notably in younger children with lower initial titres. The highest exposure rates (seroconversion or antibody boosting) were seen with SARS-CoV-2 (51 [59%] of 87), EV-D68 (36 [41%] of 87), RSV (36 [41%] of 87), and influenza (35 [40%] of 87), whereas the pathogens most frequently detected by respiratory swab sequencing were EV-D68 (clade B3), rhinovirus A, and rhinovirus C (n=7 each). Incorporating EV-D68 serological data into epidemiological models resulted in an 82% reduction in the range of prediction errors and a 33% reduction in median prediction errors for longer-term EV-D68 circulation dynamics compared with national pathogen surveillance data alone.

Interpretation

In this study, we captured immunological evidence of endemic virus re-emergence in children following lifting of pandemic NPIs, which revealed high rates of exposure to endemic respiratory pathogens in a large group of seronegative, predominantly younger, children. This study demonstrates the feasibility and utility of immunoepidemiological surveillance to enable more precise and accurate modelling of pathogen circulation dynamics to predict and prepare for future waves of disease.

Funding

Intramural Research Program of the National Institute of Allergy and Infectious Diseases–Vaccine Research Center, and the National Cancer Institute, National Institutes of Health.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00349-4/fulltext?rss=yes

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Return of the Biennial #Circulation of #Enterovirus D68 in #Colorado #Children in 2024 Following the Large 2022 #Outbreak

Abstract

Enterovirus D68 (EV-D68) caused large biennial cyclical outbreaks of respiratory disease and cases of acute flaccid myelitis from 2014 to 2018 in the USA. An anticipated outbreak did not occur in 2020, likely due to non-pharmaceutical interventions targeting the COVID-19 pandemic. A large respiratory disease outbreak occurred again in 2022, but uncertainty remained regarding if circulation of EV-D68 would return to the pre-pandemic patterns. We conducted prospective active surveillance of clinical respiratory specimens from Colorado children for EV-D68 in 2023 and 2024. A subset of residual specimens positive for rhinovirus/enterovirus (RV/EV) were tested for EV-D68 via a validated in-house EV-D68 reverse transcription–PCR assay. During epi weeks 18–44 in 2023, 525 residual specimens positive for RV/EV all tested negative for EV-D68. In 2024, during epi weeks 18–44, 10 (1.8%) of the 546 RV/EV-positive specimens were EV-D68-positive. The EV-D68-positive cases were predominantly young children (median age 4.8 years) receiving treatment with asthma medications. Following the 2022 EV-D68 outbreak, an anticipated outbreak did not occur in 2023. While EV-D68 was detected in 2024, the number of cases was not as significant as in prior outbreak years. Continued surveillance for EV-D68 will be important to understand the future dynamics of EV-D68 circulation and prepare for future outbreaks.

Source: Viruses, https://www.mdpi.com/1999-4915/17/5/673

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Sustained circulation of #enterovirus D68 in #Europe in 2023 and continued #evolution of #EVD68 B3-lineages associated with distinct amino acid substitutions in VP1 protein

Highlights

• Enterovirus D68 (EV-D68) was circulating in Europe in 2023

• Most EV-D68 cases were captured through clinical EV surveillance

• Phylogenetic analysis of the VP1 region revealed a distinct B3-derived lineage

• The identified B3 lineage presented a previously undescribed residue change, D554E

Abstract

Background

Enterovirus D68 (EV-D68) causes respiratory disease ranging from mild to severe and in rare cases a paralytic syndrome, called acute flaccid myelitis (AFM). Since the global EV-D68 outbreak in 2014, the virus has mainly circulated in biennial epidemic cycles with peaks detected during even years. However, following the COVID-19 pandemic, the seasonal pattern of EV-D68 has been characterized by large yearly upsurges. Here, we describe the circulation of EV-D68 in Europe in 2023 and track its genetic evolution.

Study design

Data was compiled from members of the European Non-Polio Network (ENPEN). This included monthly data on the total number of EV samples tested, EV positive samples, EV-D68 positive samples and cases, and other EV positive samples detected in 2023. Information on sample types and surveillance system was recorded. Sequence data from the VP1 gene was used for phylogenetic and amino acid sequence analysis.

Results

EV was detected in 13585 out of 203622 diagnostic samples tested (6.7%), of which 402 (3.0%) were determined as EV-D68, representing 386 cases. EV-D68 infections peaked in October 2023 (136/386; 35.2%). 267/386 (69.2%) of EV-D68 cases were captured through clinical EV surveillance, almost all of which (202/204 of positive samples with sample type information) were detected in respiratory specimens. Phylogenetic analysis performed on 99 VP1 sequences revealed a distinct B3-derived lineage with a previously undescribed residue change, D554E, in Europe.

Conclusions

The study documents sustained circulation of EV-D68 in Europe in 2023, the evolution of B3-derived lineages, and appearance of previously undescribed amino acid substitutions in Europe. This stresses the need for continuous EV-D68 surveillance and harmonization of EV-D68 detection practices towards better data comparability across countries.

Source: Journal of Clinical Virology, https://www.sciencedirect.com/science/article/abs/pii/S1386653225000277?dgcid=rss_sd_all

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