Search Results (55)

Enteroviruses (EVs) are small, non-enveloped RNA viruses that can cause diverse clinical outcomes, particularly severe in patients with primary immunodeficiency (PID) due to their impaired ability to clear infections. This study aimed to characterize EV excretion among 138 Tunisian PID patients over a five-year period, to identify circulating EV serotypes and assess their genetic diversity. A total of 558 stool samples were collected and analyzed by virus isolation and intratypic differentiation using RT-qPCR. Molecular typing was performed through Sanger sequencing of the VP1 region and whole genome sequencing using Next-Generation Sequencing (NGS) technologies. Phylogenetic analysis was conducted using the Maximum Likelihood (ML) method. EVs were detected in 55 stool samples from 23 patients. The excretion kinetics of EVs ranged between 30 and 946 days. Thirteen serotypes were identified, including one Poliovirus (PV) and twelve Non-Polio Enteroviruses (NPEVs), predominantly belonging to species B. Two previously unreported serotypes in Tunisia were detected: Coxsackievirus A5 (CVA5) and Echovirus type 19 (E19). In addition, five patients presented enhanced susceptibility to the excretion of successive EV serotypes, and one patient exhibited a co-infection. A possible recombination event was identified in one patient involving Coxsackievirus B5 (CVB5), Coxsackievirus A9 (CVA9) and Coxsackievirus B1 (CVB1) sequences. Phylogenetic analysis showed close genetic relationships with European, American and Asian strains. These findings underscore the dynamic nature of EV circulation and the importance of ongoing molecular surveillance to detect emerging serotypes and guide public health strategies. Full article

From July 2022, a novel Echovirus 11 (E11) variant has been associated with severe neonatal infections and liver failure. Currently, there are no vaccines or antiviral options for the targeted treatment of non-polio enterovirus (EV) infections; therefore, anti-EV drugs are urgently needed. In this study, the putative anti-E11 activity of two isoxzoline-carbocyclic monophosphate nucleotides (4a and 4b) was evaluated in vitro by cytopathic effect (CPE) reduction in VERO 76 cells and qRT-PCR. Treatment with nucleotide 4a at 25 and 50 μM successfully diminished the CPE caused by E11 by 90% and 75%, respectively, and induced a reduction in viral RNA in the supernatant by 72% and 89%. In contrast, the treatment with 25 and 50 μM of 4b caused a minor inhibition of CPE (58 and 38%), and no significant E11 RNA level changes were observed. A time course viral progeny production assay was performed to assess the inhibitory effect of nucleotide 4a on E11 infection progression. Compared to the control, the treated group showed a significant drop in viral RNA levels, with reductions of 43% at 10 h, 65% at 24 h, and 96% at 48 h post-infection. The results showed the extensive antiviral properties of the monophosphate nucleotide 4a in vitro. Moreover, a retrospective molecular docking study strongly supports that nucleotide 4a is an RdRp inhibitor capable of decreasing E11 genome replication and virus particle formation in VERO 76 cells. Full article

In this study, seven Pleosporaceae strains isolated from the seagrass Posidonia oceanica and the jellyfish Pelagia noctiluca in the central Tyrrhenian Sea were characterized using a polyphasic approach (morpho-physiological, molecular, and phylogenetic analyses). Based on multi-locus phylogenetic inference and morphological characters, a new species, Tamaricicola fenicei sp. nov. was proposed. Multi-locus phylogenetic analyses, using the nuclear ribosomal regions of DNA (nrITS1-nr5.8S-nrITS2, nrLSU, and nrSSU) as well as the rpb2 and tef-1α gene sequences, strongly supported the new taxon. The phylogenetic inference, estimated using Maximum Likelihood and Bayesian Inference, clearly indicates that Tamaricicola fenicei sp. nov. forms a distinct clade within the monospecific genus Tamaricicola. The antimicrobial activity of the chloroformic and butanolic extracts from malt agar cultures of the new species exhibited interesting antiviral and antibiofilm properties. In particular, a MIC of 3.0 µg/mL was observed against the Echovirus E11 in Vero-76 cells; moreover, a biofilm BIC₅₀ reduction at 53 µg/mL was observed against Staphylococcus aureus ATCC 25923. Full article

Enteroviruses of the Picornaviridae family are transmitted primarily by the fecal–oral route. Transmission may occur following hand contact with contaminated fomites and subsequent ingestion of virus conveyed to the mouth by the contaminated hand. The persistence of these viruses on fomites likely plays a role in this transmission scenario. Six echoviruses (1, 2, 3, 5, 6, and 7) that cause frequently reported clinical cases in the United States were studied, along with poliovirus type 1 vaccine strain LSc-2ab. The infectivity half-lives of the enteroviruses deposited on vinyl tile coupons in a 10% fecal solution ranged from 1.7 to 12.6 h. The echovirus serotypes most commonly associated with reported infections persisted longer on the vinyl tiles than the less commonly reported types. This increased persistence on surfaces may favor the transmission of these echoviruses through the fecal–oral route. These results inform the future selection of appropriate model enteroviruses for challenging newly formulated and eco-friendly disinfectants or other strategies in infection prevention and control for enteroviruses. Full article

Echovirus 18, a member of the B group of enteroviruses, is a significant etiological agent of aseptic meningitis and viral encephalitis in children. In this study, we investigated the pathogenicity of E18 by establishing a mouse infection model after comparing various mouse strains and injection methods. Two-day-old IFNAR1 knockout mice infected with clinical isolates of E18 exhibited symptoms such as lethargy, hind limb paralysis, and even mortality. Similarly, some two-day-old C57BL/6J mice displayed comparable symptoms; however, the incidence was lower than that observed in IFNAR1 knockout mice. No similar symptoms were noted in any Balb/c mice. Significant pathological changes were observed in skeletal muscle, brain tissue, and other organs of symptomatic mice; among these tissues, skeletal muscle demonstrated the highest viral load. The established infection model using two-day-old IFNAR1 knockout mice provides valuable insights into further investigations regarding its pathological injury mechanisms as well as the protective effects conferred by antibodies. Full article

Echovirus 30 (E-30), a member of the Enterovirus B species, is frequently linked to neurological illnesses such as aseptic meningitis, encephalitis, and hand, foot, and mouth disease. In this study, we present the complete-genome analysis of an Echovirus 30 strain isolated from cerebrospinal fluid (CSF) and stool samples of a pediatric encephalitis case in Kerala, India, during 2023. A comparative genomic investigation was carried out using a dataset of 111 human E-30 isolates, encompassing 116,991 mutation records. This analysis revealed six distinct non-synonymous amino acid substitutions uniquely present in the isolate PQ472410.1, which may be associated with pathogenicity and/or neurotropic behavior. To the best of our knowledge, this represents the first complete-genome sequence report of E-30 from an encephalitis case in India. These findings contribute valuable information to the understanding of E-30’s molecular epidemiology and evolution and offer vital data for enhancing surveillance and response strategies against enteroviral infections. Full article

Non-pathogenic natural and recombinant strains of human Enteroviruses are the subject of ongoing study with some strains having been approved for use as anticancer agents. The efficacy of oncolytic virotherapy depends upon identifying the receptor utilized by a specific strain for cell entry, and the presence of this receptor on the surface of cancer cells. Accordingly, a rapid and straightforward approach to determining the enteroviral receptors is necessary for developing an effective patient-specific, virus-based cancer therapy. To this end, we created a panel of seven lines with double knockouts on the background of the HEK293T cell line, which lacks the IFNAR1 gene. In these lines, the main viral receptor genes, including PVR, CXADR, CD55, ITGA2, SCARB2, ICAM1, and FCGRT, were knocked out using the CRISPR/Cas9 system. The panel of lines was validated on twelve different Enteroviruses types, providing a basis for studying the molecular mechanisms of enterovirus entry into cells, and for developing new therapeutic strains. Full article

Enteric virus infection is a major public health issue worldwide. Enteric viruses have become epidemic infectious diseases in several countries. Enteric viruses primarily infect the gastrointestinal tract and complete their life cycle in intestinal epithelial cells. These viruses are transmitted via the fecal–oral route through contaminated food, water, or person to person and cause similar common symptoms, including vomiting, abdominal pain, and diarrhea. Diarrheal disease is the third leading cause of death in children under five years of age, accounting for approximately 1.7 billion cases and 443,832 deaths annually in this age group. Additionally, some enteric viruses can invade other tissues, leading to severe conditions and even death. The pathogenic mechanisms of enteric viruses are also unclear. In this review, we organized the research on trending enteric virus infections, including rotavirus, norovirus, adenovirus, Enterovirus-A71, Coxsackievirus A6, and Echovirus 11. Furthermore, we discuss the gastrointestinal effects and pathogenic mechanisms of SARS-CoV-2 in intestinal epithelial cells, given the gastrointestinal symptoms observed during the COVID-19 pandemic. We conducted a literature review on their pathogenic mechanisms, which serves as a guide for formulating future treatment strategies for enteric virus infections. Full article

Echovirus 11 has emerged as a major public health concern, causing sepsis in neonates in many European countries in recent years. In Africa, especially West Africa, where resources and diagnostic capacities are limited, only sporadic cases have been reported. To better understand the recent molecular epidemiology of E11 in West Africa, we characterized twenty-three echovirus 11 strains isolated through the acute flaccid paralysis and environmental surveillance systems for polio from 2013 to 2023, using high-throughput sequencing. Our data are noteworthy due to identifying for the first time a recombinant strain from an acute flaccid paralysis case and represent the first focus to date on molecular characterization of echovirus 11 in West Africa. Moreover, our data show that echovirus 11 diverged from 1970 (95% HPD range, 1961–1979) and evolved into four distinct clades, with the virus spread from West Africa to Europe, exhibiting two introductions in France around 2017, from Senegal and Guinea. Furthermore, the in silico analysis reveals four non-conservative amino acid substitutions in the VP1 sequences of the European strains associated with neonatal sepsis in newborns and a conserved amino acid motif in the VP1 protein toward enterovirus genotypes. Our data provide new insights into the epidemiology of echovirus 11 and point to the crucial need to implement specific surveillance programs targeting non-polio enteroviruses for the rapid identification of emerging or re-emerging enterovirus species, particularly in Africa. Full article

Enteroviruses, with their diverse clinical manifestations ranging from mild or asymptomatic infections to severe diseases such as poliomyelitis and viral myocarditis, present a public health threat. However, they can also be used as oncolytic agents. This review shows the intricate relationship between enteroviruses and host cell factors. Enteroviruses utilize specific receptors and coreceptors for cell entry that are critical for infection and subsequent viral replication. These receptors, many of which are glycoproteins, facilitate virus binding, capsid destabilization, and internalization into cells, and their expression defines virus tropism towards various types of cells. Since enteroviruses can exploit different receptors, they have high oncolytic potential for personalized cancer therapy, as exemplified by the antitumor activity of certain enterovirus strains including the bioselected non-pathogenic Echovirus type 7/Rigvir, approved for melanoma treatment. Dissecting the roles of individual receptors in the entry of enteroviruses can provide valuable insights into their potential in cancer therapy. This review discusses the application of gene-targeting techniques such as CRISPR/Cas9 technology to investigate the impact of the loss of a particular receptor on the attachment of the virus and its subsequent internalization. It also summarizes the data on their expression in various types of cancer. By understanding how enteroviruses interact with specific cellular receptors, researchers can develop more effective regimens of treatment, offering hope for more targeted and efficient therapeutic strategies. Full article

Enteroviruses are RNA viruses that initiate infections through the gastrointestinal (GI) tract and are associated with enteric illness in individuals of all ages. Most serious infections of enteroviruses are in infants and young children where it is the common cause of aseptic meningitis and other systemic diseases, leading to a high mortality rate. Enteroviruses belong to the small non-enveloped family of the Picornaviridae family. The virus can spread mainly through fecal–oral and respiratory routes. In the Arabian Gulf countries, the incidence of enteroviral infections is only restricted to a few reports, and thus, knowledge of the epidemiology, characteristics, and pathogenesis of the virus in the gulf countries remains scarce. In this minireview, we sought to provide an overview of the characteristics of enterovirus and its pathogenesis, in addition to gathering the reports of enterovirus infection prevalence in Gulf Cooperation Council (GCC) countries. We also present a summary of the common methods used in its detection. Full article

After the first phase of the COVID-19 pandemic in Europe, a new highly pathogenic variant of echovirus 11 (E11) was detected. The aim of this study was to analyze the genetic diversity of Polish E11 environmental and clinical strains circulating between 2017 and 2023 as well as compare them with E11 strains isolated from severe neonatal sepsis cases reported in Europe between 2022 and 2023. Additionally, the study explores the effectiveness of environmental monitoring in tracking the spread of new variants. For this purpose, the complete sequences of the VP1 capsid protein gene were determined for 266 E11 strains isolated in Poland from 2017 to 2023, and phylogenetic analysis was performed. In the years 2017–2023, a significant increase in the detection of E11 strains was observed in both environmental and clinical samples in Poland. The Polish E11 strains represented three different genotypes, C3, D5 and E, and were characterized by a high diversity. In Poland, the intensive circulation of the new variant E11, responsible for severe neonatal infections with a high mortality in Europe, was detected in the years 2022–2023. This investigation demonstrates the important role of environmental surveillance in the tracking of enteroviruses circulation, especially in settings with limited clinical surveillance. Full article

In 2018, an increase in echovirus 30 (E30) detections was reported in some European countries. To assess the circulation and phylogenetic relationships of E30 in Bulgaria, E30 samples identified at the National Reference Laboratory for Enteroviruses, National Centre of Infectious and Parasitic Diseases, Bulgaria (NRL for Enteroviruses) in 2017 and 2018 were subjected to sequencing and phylogenetic analysis. The present study revealed that sample positivity did not significantly increase in Bulgaria during the European upsurge. E30 was identified in six patients, two of whom were epidemiologically linked. The maximum-likelihood phylogenetic tree showed that sequences from five patients belonged to the G1 lineage (clades G1a and G1b). The sequence from one patient belonged to the G2 lineage and was grouped closer to sequences from the last E30 outbreak in Bulgaria in 2012. No recombination events were detected. The European E30 upsurge in 2018 was caused by two clades, and one of them was G1. The fact that the majority of the Bulgarian samples belonged to G1 indicated that the virus was present in the country but did not cause a local upsurge. Phylogenetic and epidemiological data indicated sporadic E30 cases and a possible shift towards G1 lineage in 2017 and 2018. Full article

Enteroviruses (EVs) represent a major cause of viral meningitis, being responsible for nearly 1 billion infections each year worldwide. Several techniques were developed to obtain better diagnostic results of EV infections. Herein, we evaluated the efficiency of EV detection through isolation on both Rhabdomyosarcoma (RD) and Vero cell line cultures, conventional reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR. Thus, 50 cerebrospinal fluid (CSF) samples belonging to patients suspected to have viral meningitis in northern Algeria were collected, anonymously numbered from 1 to 50 and subjected to the above-mentioned techniques for EV detection. Using real-time RT-PCR, 34 CSF samples were revealed to be positive for viral origin of meningitis (68%). Thirteen of them were positive when the conventional RT-PCR was used (26%), and only three samples gave positive results when the cell culture technique was used (6%). Surprisingly, two cell culture-positive CSF samples, namely, 31 and 39, were negative using RT-PCR directly on the original samples. However, they turned to be positive when amplification was carried out on their corresponding cell culture supernatant. The cell-cultured viral isolates were then identified by sequencing their viral genome’s VP1 regions. All of them were revealed to belong to the echovirus 27 strain. This investigation demonstrates that RT-PCR techniques are often more sensitive, accurate and much faster, providing reliable results within a clinically acceptable timeframe. However, viral isolation on cell cultures remains crucial to obtain enough viral load for serological tests or even to avoid the rare, but existing, false negative PCR. Full article

Alphaviruses, belonging to the Togaviridae family, and bunyaviruses, belonging to the Paramyxoviridae family, are globally distributed and lack FDA-approved vaccines and therapeutics. The alphaviruses Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV) are known to cause severe encephalitis, whereas Sindbis virus (SINV) causes arthralgia potentially persisting for years after initial infection. The bunyavirus Rift Valley Fever virus (RVFV) can lead to blindness, liver failure, and hemorrhagic fever. Brilacidin, a small molecule that was designed de novo based on naturally occurring host defensins, was investigated for its antiviral activity against these viruses in human small airway epithelial cells (HSAECs) and African green monkey kidney cells (Veros). This testing was further expanded into a non-enveloped Echovirus, a Picornavirus, to further demonstrate brilacidin’s effect on early steps of the viral infectious cycle that leads to inhibition of viral load. Brilacidin demonstrated antiviral activity against alphaviruses VEEV TC-83, VEEV TrD, SINV, EEEV, and bunyavirus RVFV. The inhibitory potential of brilacidin against the viruses tested in this study was dependent on the dosing strategy which necessitated compound addition pre- and post-infection, with addition only at the post-infection stage not eliciting a robust inhibitory response. The inhibitory activity of brilacidin was only modest in the context of the non-enveloped Picornavirus Echovirus, suggesting brilacidin may be less potent against non-enveloped viruses. Full article