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PubMed2025

Global Evolution and Transmission Dynamics of Enterovirus D68.

Enterovirus D68 (EV-D68), a serotype of the enterovirus species D, has garnered significant attention due to outbreaks reported in 2014, 2016, and 2018. In this study, 36 Chinese EV-D68 strains were isolated, sequenced, and combined with all EV-D68 VP1 sequences from GenBank to form a data set of 1679 sequences. This data set served as the basis for phylogenetic, evolutionary dynamics, phylogeographic, and key amino acid site mutation analyses of EV-D68. Based on the VP1 region, EV-D68 is classified into four genotypes (A-D), and seven subgenotypes (B1-B3, D1-D4), with B3 and D3 being the predominant subgenotypes. Bayesian skyline plots indicated that genotypes B and D experienced multiple population expansions, aligning with reported EV-D68 outbreaks. Phylogeographic analyses of the B3 subgenotypes revealed sequences from Europe and North America clustering into a single evolutionary branch, suggesting significant transmission between these regions. Additionally, mutation analysis identified VP1-98 as a high-frequency mutation site, differing significantly between the previously prevalent A and C genotypes and the currently prevalent B and D genotypes. However, the functional implications of this mutation require further investigation. This study provides a solid theoretical basis for epidemiological research, disease surveillance, and prevention efforts related to EV-D68.

Enterovirus Infections↗
PubMed2025

Outbreak of Enterovirus D68 in Young Children, Brescia, Italy, August to November 2024.

Enterovirus D68 (EV-D68) is responsible for a plethora of clinical manifestations ranging from asymptomatic infections to severe respiratory symptoms and neurological disorders. EV-D68 was first detected in children with pneumonia in 1962 and, from then, only sporadic cases were reported until 2014, when outbreaks were notified across the world. After the withdrawal of preventive measures against SARS-CoV-2, a significant increase in EV-D68 infections has been reported in 2021-2022. A surveillance program to evaluate the incidence of enterovirus/rhinovirus (EV/RV) infections was implemented at the Brescia Civic Hospital, Italy. Fifty-five EV/RV-positive respiratory samples, belonging to pediatric patients, were subjected to NGS. We observed that 61.8% of samples were positive for EV, with EV-D68 as the most prevalent genotype predominantly detected between August and November 2024. Phylogenetic analysis revealed that EV-D68 sequences formed two monophyletic clades corresponding to the A2 and B3 lineages, highlighting their recent introduction in Italy. Interestingly, 40% of pediatric EV-D68 infections were detected with at least one other EV/RV. Our study highlights the crucial role played by genomic surveillance of respiratory infections to monitor the circulation of emerging and re-emerging viruses, as well as their evolution. This will be fundamental to enable prompt intervention strategies.

Humans↗
PubMed2026

Genomic surveillance of enterovirus D68 circulating in 2025 reveals the emergence of a novel A2/B3 recombinant lineage.

Enterovirus D68 (EV-D68) has re-emerged over the past decade as a significant respiratory pathogen associated with severe respiratory disease and acute flaccid myelitis. Its circulation has typically followed a biennial pattern, with predominance in late summer and early fall, a pattern that was temporarily disrupted during the COVID-19 pandemic. Surveillance in 2025 revealed off-season circulation of EV-D68. This study describes the genomic characteristics of the 2025 EV-D68 viruses and the clinical features of affected patients. Between May and December 2025, remnant respiratory specimens positive for rhinovirus/enterovirus were screened for EV-D68 and subjected to whole-genome sequencing. Phylogenetic analyses were performed using maximum-likelihood methods. Recombination was assessed using subgenomic phylogenies, SimPlot similarity and BootScan analyses, and read-level inspection. Among 1,321 patients tested, 147 (11.1%) were EV-D68-positive, and 119 (81.0%) yielded complete genomes. EV-D68 positivity increased in July 2025, peaked in August (~21%), and remained elevated through September and October, exceeding levels observed in 2024. Patients had a median age of 36 years, with infections disproportionately affecting older adults. Phylogenetic analysis demonstrated exclusive circulation of subclade A2. Five genomes formed a distinct recombinant lineage (A2-Re). Subgenomic phylogenies showed clustering with A2 viruses in the P1 region and with B3 viruses in the P2-P3 regions. SimPlot and BootScan analyses identified a recombination breakpoint near the 2A/2B junction (~nt 3,700). The recombinant lineage was associated with temporally clustered cases in September-October. These findings demonstrate recombination between distinct EV-D68 subclades and underscore the importance of whole-genome surveillance for accurate viral characterization. Continued genomic monitoring is essential for detecting emerging variants with potential implications for transmissibility, pathogenicity, and public health preparedness.IMPORTANCEThis study highlights an increased off-season circulation of Enterovirus D68 (EV-D68) and a higher burden of disease in adults in 2025. The identification of a novel A2-B3 recombinant lineage provides evidence of ongoing viral evolution through recombination, a mechanism that may alter transmissibility, virulence, or immune responses. Detection of this lineage in temporally clustered cases suggests local transmission and underscores the potential for rapid spread of newly emerged variants. These findings emphasize the limitations of partial genomic approaches and the critical role of whole-genome sequencing in accurately characterizing circulating strains and identifying recombination events. Enhanced genomic surveillance is essential to detect emerging variants in real time, inform diagnostic assay performance, and support public health responses. Continued monitoring of EV-D68 evolution will be important for anticipating changes in disease burden, guiding clinical awareness, and strengthening preparedness for future outbreaks.

Humans↗
PubMed2025

EV-D68 cleaves LARP1 and PABPC1 by 3Cpro to redirect host mRNA translation machinery toward its genomic RNA.

Enterovirus D68 (EV-D68) is an emerging pathogen associated with severe respiratory diseases and neurological complications, such as acute flaccid myelitis. EV-D68 has developed sophisticated mechanisms to hijack host translation machinery, facilitating its replication and impairing host mRNA translation. In this study, we demonstrate that EV-D68 cleaves La-related protein 1 (LARP1) and poly(A)-binding protein cytoplasmic 1 (PABPC1) through its proteases 3Cpro and 2Apro. Our results indicate that overexpressing LARP1 and PABPC1 significantly inhibits EV-D68 replication and reduces the virus-mediated suppression of host translation. While both LARP1 and PABPC1 regulate translation, they exert antiviral effects through distinct mechanisms. We found that LARP1 interacts with the 5'UTR of EV-D68 RNA through its LAM domain, and this interaction is crucial for its antiviral function. LARP1 translation modulation is also influenced by the mTOR and CDK1 signaling pathways. Viral infection inhibits mTOR and CDK1 phosphorylation, which enhances LARP1's binding to viral RNA and inhibits viral translation. To counteract this inhibition, EV-D68 cleaves LARP1 through 3Cpro, thereby promoting efficient viral translation. We also investigated other enteroviruses, such as EV-A71 and CV-A16, which similarly target LARP1 and PABPC1, indicating a conserved mechanism across enteroviruses. Our findings offer new insights into how EV-D68 manipulates host translation and highlight the potential of targeting LARP1 and PABPC1 for antiviral interventions.

Humans↗
PubMed1976

Measurements of the prevalence of viral infections.

Viral diseases exert their major impact through morbidity, impairment of personal health, loss of time at work and school, and cost of medical care. Relatively few of the known viruses cause a significant number of deaths; influenza, childhood viral pneumonia, and hepatitis are the only viral diseases causing more than 1,000 deaths per year. Data based on the National Health Interview Survey of the National Center for Health Statistics show that the common cold annually causes 35.6 acute illnesses per 100 persons. The data reported by the National Therapeutic Disease Index (on the basis of visits by patients to a sample of 1,500 private physicians) show that influenza and other acute respiratory conditions account for about one-third of all visits to physicians. Nearly all viruses first infect humans in infancy and childhood, with a relatively low fatality rate but with frequent episodes of illness.

Adenoviridae↗
PubMed1977

The viral etiology of acute respiratory infections in children in Uganda.

The role of viruses in respiratory diseases of young children in Uganda was studied. A viral etiology was established in 36% of the infections investigated. The most important pathogens were found to be respiratory syncytial virus and parainfluenza viruses, which were responsible for 26% of infections investigated. They caused both upper and lower respiratory tract diseases. There was little or no seasonal variation in the etiology of these infections. Adenoviruses were found to be less important and were etiologically related to only 4% of respiratory disease cases. Influenza viruses and enteroviruses were also found to be associated with respiratory infections. However, they were less frequent and their role was insignificant. The role of multiple virus infections was also insignificant.

Acute Disease↗
PubMed1979

Easily hydrolyzable, water-soluble derivatives of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazoline-4-one, a novel antiviral compound.

The preparation of a series of indole N-acyl and N-carbamic esters of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazolin-4-one (1) is reported. These derivatives were synthesized as potential water-soluble precursors of the antiviral thiazolinone 1, for evaluation by intranasal administration against influenza and other respiratory infections caused by viruses. Salts of the basic carbamic esters (16--19) possess the required water solubility, undergo rapid hydrolysis and decarboxylation at pH values greater than 6, and have high activity against influenza A2 and Coxsackie B1 viruses in vitro. In influenza A2 infected ferrets a representative ester (16) reduced the severity and duration of disease symptoms and reduced nasal wash virus titres but caused local irritancy.

Animals↗
PubMed1976

Effect of acid pH, salts, and temperature on the infectivity and physical integrity of enteroviruses.

At 2 degrees and 30 degrees C, enteroviruses are more stable on the acid than on the alkaline side of neutrality. In the range from pH 3 to 9, temperature is so influential that the fastest inactivation rate at 2 degrees C is slower than the slowest inactivation rate at 30 degrees C. Specific ions or salts also affect the rate of inactivation of enteroviruses. NaCl and other chloride salts enhance the inactivation of poliovirus at pH 3. NaCl is considerably less effective against poliovirus in the range of pH 4.5 to 7.0 than at pH less than 4.5. Loss of RNA infectivity of the virus particle proceeds as rapidly as the loss of infectivity of the particle itself, except at pH 3 in the presence of MgCl2. Inactivation results in alterations to the physical integrity of enteroviruses. At pH 5 and 7, RNA hydrolysis of poliovirus particles occurs; and at pH3, 5,6, and 7 the nucleic acid becomes susceptible to ribonuclease. Only virus particles inactivated at pH 3 show a sensitivity to chymotrypsin. The hemagglutinins of echovirus type 7 are destroyed during inactivation at pH 3,4,5, and 6; but at pH 6 this alteration precedes the loss of infectivity. The pH of the suspension is a primary determinant of the mechanism of virus destruction and possibly of the loss of infectivity at these temperatures.

Cell Line↗
PubMed1978

Potentiation of coxsackievirus B3 infection in adult mice pretreated with a gold salt.

In mice treated with sodium aurothiomalate (myocrisin), prior to infection with Coxsackievirus B3, 90% of the animals died by the 11th day postinfection (p.i.). A mortality of 10% was noted in mice receiving myocrisin only, and no deaths occurred in animals infected with virus alone. The highest amount of virus was recovered from the pancreas of myocrisin-treated mice on day 3 p.i. This was over 500-fold higher than the virus titer found in the pancreas of mice infected with virus only. Generally the titer of virus present in different organs was higher at every point in drug-treated animals as compared to intact mice infected with the virus. A high and persistent viremia was present in myocrisin-treated mice; in contrast a low viremia followed by virus clearance from the blood was observed in intact mice infected with the virus. The antibody response was studied in intact and myocrisin-treated mice infected with the virus. In both groups, no neutralizing antibodies were detected on days 1, 2, and 3 p.i. On day 7 after infection, the titers of antibodies were 1:16 and 1:12 in intact and myocrisin-treated mice, respectively. Administration of hyperimmune anti-Coxsackievirus B3 serum 6 hours after infection protrected in myocrisin-treated group of mice against lethal disease. The results of these studies suggest that (1) antibodies alone may not be sufficient to limit the spread and persistence of virus in natural infections and (2) in the absence of any apparent histopathological differences the increased multiplication of Coxsackievirus B3 could be the cause of death in myocrisin-treated mice.

Animals↗
PubMed1978

Coxsackie myocarditis complicating treatment of Hodgkin's lymphoma.

A fatal case of Coxsackie B4 myocarditis complicating treatment of Hodgkin's lymphoma in an adult is reported. The virus was isolated from the myocardium obtained at autopsy and light microscopy confirmed a myocarditis with involvement of the conduction system. Electron-microscopy showed dense mitochondrial inclusions. Coxsackie myocarditis rarely results in death of affected adults. It is postulated in this case that the treatment of the Hodgkin's lymphoma resulted in B lymphocyte depletion, allowing a more virulent infection to occur with resultant fatal myocarditis.

Adult↗
PubMed1978

Inactivation of enteroviruses by ascorbic acid and sodium bisulfite.

Poliovirus type 1, coxsackievirus type A9, and echovirus type 7 were inactivated by sodium bisulfite and ascorbic acid. Inactivation rates depended upon concentration, temperature, and pH. RNA infectivity was lost during inactivation; the capsid was also altered by these inactivating agents, as determined by enzyme sensitivity assays and by tests of adsorption to cells. Structural modifications of the virus particles were not identical, suggesting that the mechanism of inactivation by ascorbic acid differs from that of sodium bisulfite.

Ascorbic Acid↗