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Future Microbiology 2015Viruses such as coxsackievirus B3 (CVB3) are entirely host cell-dependent parasites. Indeed, they must cleverly exploit various compartments of host cells to complete... (Review)
Review
Viruses such as coxsackievirus B3 (CVB3) are entirely host cell-dependent parasites. Indeed, they must cleverly exploit various compartments of host cells to complete their life cycle, and consequently launch disease. Evolution has equipped this pico-rna-virus, CVB3, to use different strategies, including CVB3-induced direct damage to host cells followed by a host inflammatory response to CVB3 infection, and cell death to super-additively promote target organ tissue injury, and dysfunction. In this update, the patho-stratagems of CVB3 are explored from molecular, and systems-level approaches. In summarizing recent developments in this field, we focus particularly on mechanisms by which CVB3 can harness different host cell processes including kinases, host cell-killing and cell-eating machineries, matrix metalloproteinases and miRNAs to promote disease.
Topics: Enterovirus B, Human; Host-Pathogen Interactions; Humans; Virulence; Virus Replication
PubMed: 25865198
DOI: 10.2217/fmb.15.5 -
Future Microbiology Sep 2010Coxsackieviruses are important human pathogens, and their interactions with the innate and adaptive immune systems are of particular interest. Many viruses evade some... (Review)
Review
Coxsackieviruses are important human pathogens, and their interactions with the innate and adaptive immune systems are of particular interest. Many viruses evade some aspects of the innate response, but coxsackieviruses go a step further by actively inducing, and then exploiting, some features of the host cell response. Furthermore, while most viruses encode proteins that hinder the effector functions of adaptive immunity, coxsackieviruses and their cousins demonstrate a unique capacity to almost completely evade the attention of naive CD8(+) T cells. In this artcle, we discuss the above phenomena, describe the current status of research in the field, and present several testable hypotheses regarding possible links between virus infection, innate immune sensing and disease.
Topics: Adaptive Immunity; Animals; Antibodies, Viral; Child; Child, Preschool; Coxsackievirus Infections; Enterovirus B, Human; Host-Pathogen Interactions; Humans; Immunity, Innate; Infant; Infant, Newborn; T-Lymphocytes
PubMed: 20860480
DOI: 10.2217/fmb.10.101 -
Journal of Thrombosis and Haemostasis :... Feb 2015To further understand the role of platelets in the pathogenesis of viral infections we explored platelet interaction with Coxsackieviruses B (CVB) 1 and 3. CVB is a...
BACKGROUND
To further understand the role of platelets in the pathogenesis of viral infections we explored platelet interaction with Coxsackieviruses B (CVB) 1 and 3. CVB is a group of viruses that cause the majority of human enterovirus-related viral myocarditis; their receptor (CAR) is expressed on the platelet surface and there is a well-characterized CVB3-induced myocarditis murine model.
METHODS
Human platelets were infected with CVB1 and 3 and viruses were detected in pellets and in supernatants. C57BL/6J mice with or without platelet depletion were inoculated with CVB3 and peripheral blood and heart samples collected at different times post-infection.
RESULTS
CVB1 and 3 RNA and a capsid protein were detected in infected platelets. Despite the fact that titration assays in Vero cells showed increasing infectivity titers over time, supernatants and pellets from infected platelets showed similar levels, suggesting that platelets were not susceptible to a replicative infectivity cycle. CVB binding was CAR-independent and resulted in P-selectin and phosphatidylserine (PS) exposure. CVB3-infected mice showed a rapid thrombocytopenia that correlated with an increase in platelet PS exposure and platelet-leukocyte aggregates without modification of platelet P-selectin expression or von Willebrand factor levels. Mortality, viremia, heart viral titers and myocarditis were significantly higher in platelet-depleted than normal animals. Type I IFN levels were not changed but IgG levels were lower in infected and platelet-depleted mice.
CONCLUSIONS
Our data reveal that platelets play a critical role in host survival and immune response against CVB3 infection.
Topics: Animals; Blood Platelets; Capsid Proteins; Chlorocebus aethiops; Coxsackievirus Infections; Disease Models, Animal; Enterovirus B, Human; Female; Host-Pathogen Interactions; Humans; Immunoglobulin G; Male; Mice, Inbred C57BL; Myocarditis; P-Selectin; Phosphatidylserines; RNA, Viral; Thrombocytopenia; Time Factors; Vero Cells; Virus Replication
PubMed: 25393316
DOI: 10.1111/jth.12782 -
Viruses Dec 2015Enterovirus B species (EV-B) are responsible for a vast number of mild and serious acute infections. They are also suspected of remaining in the body, where they cause... (Review)
Review
Enterovirus B species (EV-B) are responsible for a vast number of mild and serious acute infections. They are also suspected of remaining in the body, where they cause persistent infections contributing to chronic diseases such as type I diabetes. Recent studies of the infectious entry pathway of these viruses revealed remarkable similarities, including non-clathrin entry of large endosomes originating from the plasma membrane invaginations. Many cellular factors regulating the efficient entry have recently been associated with macropinocytic uptake, such as Rac1, serine/threonine p21-activated kinase (Pak1), actin, Na/H exchanger, phospholipace C (PLC) and protein kinase Cα (PKCα). Another characteristic feature is the entry of these viruses to neutral endosomes, independence of endosomal acidification and low association with acidic lysosomes. The biogenesis of neutral multivesicular bodies is crucial for their infection, at least for echovirus 1 (E1) and coxsackievirus A9 (CVA9). These pathways are triggered by the virus binding to their receptors on the plasma membrane, and they are not efficiently recycled like other cellular pathways used by circulating receptors. Therefore, the best "markers" of these pathways may be the viruses and often their receptors. A deeper understanding of this pathway and associated endosomes is crucial in elucidating the mechanisms of enterovirus uncoating and genome release from the endosomes to start efficient replication.
Topics: Endocytosis; Endosomes; Enterovirus B, Human; Host-Pathogen Interactions; Virus Attachment; Virus Internalization
PubMed: 26690201
DOI: 10.3390/v7122945 -
Virology Journal Jun 2022Echovirus 9 (E9) is associated with a wide variety of diseases and medical conditions, and the clinical symptoms of sporadic cases caused by E9 often are severe. With a...
BACKGROUND
Echovirus 9 (E9) is associated with a wide variety of diseases and medical conditions, and the clinical symptoms of sporadic cases caused by E9 often are severe. With a high global prevalence, E9 has caused multiple outbreaks worldwide. However, little is known about the genetic and geographic population dynamics of E9.
METHOD
A total of 131 VP1 gene sequences, including15 generated in this study and 116 obtained from GenBank, were used to coestimate time-resolved phylogenies to infer viral evolution and transmission in worldwide. Overlapping fragments representing whole genomes were amplified by reverse transcription polymerase chain reaction (RT-PCR) using specific primers. Then, we reported the genetic characteristics of fifteen E9 strains in the Chinese Mainland. Similarity plots and bootscanning analysis were used to determine recombination patterns of E9.
RESULTS
The estimated mean evolutionary rate of global E9 VP1 gene was 4.278 × 10 substitutions per site per year (95% confidence interval [CI], 3.822 × 10/site/year to 4.710 × 10/site/year), and the common ancestor of E9 likely emerged around 1868 (95% CI, 1840 to 1892). The full-length genomic sequences of the fifteen E9 strains showed 76.9-79.6% nucleotide identity and 95.3-95.9% amino acid identity with E9 Barty strain. 11 of 15 E9 whole genome sequence present four recombination patterns, and E9 recombinants have extensive genetic exchanges in the 2C and P3 regions with other Enterovirus B (EV-B) circulated in China. Four of six E9 strains were temperature sensitive, and two were temperature resistant, and a comparative genomics analysis suggested that 411, 865 and 867 amino acid substitution in the P1 region was related to temperature sensitivity.
CONCLUSION
This study highlights a persistent transmission network of E9 in worldwide, provides valuable information regarding the molecular epidemiology of E9.
Topics: China; Echovirus 9; Enterovirus B, Human; Evolution, Molecular; Genome, Viral; Phylogeny; Recombination, Genetic
PubMed: 35659318
DOI: 10.1186/s12985-022-01820-3 -
Journal of Virology Jul 1999
Review
Topics: 5' Untranslated Regions; Animals; Cell Membrane; Echovirus Infections; Enterovirus B, Human; Humans; Nucleic Acid Conformation; Picornaviridae; Protein Processing, Post-Translational; Viral Proteins
PubMed: 10364270
DOI: 10.1128/JVI.73.7.5249-5254.1999 -
Viruses Nov 2022Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause...
Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. Decay-accelerating factor (DAF, also known as CD55) is an attachment receptor for E11. Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1-4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). SCRs 3 and 4 of DAF interact with E11 at the southern rim of the canyon via the VP2 EF and VP3 BC loops. We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. DAF is a receptor for at least 20 enteroviruses and we classify its binding patterns from reported DAF/virus complexes into two distinct positions and orientations, named as E6 and E11 poses. Whilst 60 DAF molecules can attach to the virion in the E6 pose, no more than 30 can attach to E11 due to steric restrictions. Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier.
Topics: Infant, Newborn; Humans; Cryoelectron Microscopy; CD55 Antigens; Enterovirus; Enterovirus B, Human; Enterovirus Infections
PubMed: 36560629
DOI: 10.3390/v14122625 -
Virology Jan 2017Study of coxsackievirus B3 strain 28 (CVB3/28) stability using MOPS to improve buffering in the experimental medium revealed that MOPS (3-morpholinopropane-1-sulfonic...
Study of coxsackievirus B3 strain 28 (CVB3/28) stability using MOPS to improve buffering in the experimental medium revealed that MOPS (3-morpholinopropane-1-sulfonic acid) increased CVB3 stability and the effect was concentration dependent. Over the pH range 7.0-7.5, virus stability was affected by both pH and MOPS concentration. Computer-simulated molecular docking showed that MOPS can occupy the hydrophobic pocket in capsid protein VP1 where the sulfonic acid head group can form ionic and hydrogen bonds with Arg95 and Asn211 near the pocket opening. The effects of MOPS and hydrogen ion concentrations on the rate of virus decay were modeled by including corresponding parameters in a recent kinetic model. These results indicate that MOPS can directly associate with CVB3 and stabilize the virus, possibly by altering capsid conformational dynamics.
Topics: Capsid Proteins; Enterovirus B, Human; Enterovirus Infections; Humans; Hydrogen-Ion Concentration; Molecular Docking Simulation; Morpholines
PubMed: 27940223
DOI: 10.1016/j.virol.2016.12.002 -
Molecules (Basel, Switzerland) Mar 2020Coxsackievirus B3 (CVB3) is the most common cause of acute and chronic viral myocarditis, primarily in children, while human adenovirus infections represent a...
Coxsackievirus B3 (CVB3) is the most common cause of acute and chronic viral myocarditis, primarily in children, while human adenovirus infections represent a significant cause of morbidity and mortality worldwide, in people of all ages. A series of novel 2-benzoxyl-phenylpyridine derivatives were evaluated for their potential antiviral activities against CVB3 and adenovirus type 7 (ADV7). Preliminary assays indicated that some of these compounds exhibited excellent antiviral effects on both CVB3 and ADV7 viruses; they could effectively inhibit virus-induced cytopathic effects, reduce viral progeny yields, and had similar or superior antiviral activities compared with the control drug, ribavirin. Further, these compounds targeted the early stages of CVB3 replication in cells, including viral RNA replication and protein synthesis, rather than inactivating the virus directly, inhibiting virus adsorption/entry, or affecting viral release from cells. Our data demonstrate that the tested 2-benzoxyl-phenylpyridine derivatives are effective inhibitors of CVB3 and ADV7, raising the possibility that these compounds might be feasible candidates for anti-viral agents.
Topics: Adenoviruses, Human; Antiviral Agents; Enterovirus B, Human; HeLa Cells; Humans; Molecular Structure; Pyridines; Virus Internalization; Virus Replication
PubMed: 32204528
DOI: 10.3390/molecules25061409 -
Epidemiology and Infection Sep 2017Pakistan is at the verge of polio eradication but isolation of non-polio enteroviruses (NPEVs) from acute flaccid paralysis (AFP) cases may result in serious or even...
Pakistan is at the verge of polio eradication but isolation of non-polio enteroviruses (NPEVs) from acute flaccid paralysis (AFP) cases may result in serious or even fatal outcome. Many enteroviruses share similar symptoms and epidemiology as is the case with poliovirus and coxsackievirus (CV). The present study was designed to genetically characterize coxsackievirus B (CV-B) serotypes isolated from non-polio acute flaccid paralytic children, as well as to understand their probable role in paralysis. A total of 63 (20·1%) out of 313 stool samples during 2013 were found positive for NPEVs in rhabdomyosarcoma cells. Only 24 (38·0%) NPEVs were typed as CV-B by microneutralization assay and were further characterized by sequencing of the viral protein 1 (VP1) gene. Molecular phylogenetic analyses classified the study strains into six coxsackievirus B serotypes (coxsackievirus B1 to B6) with their respective prototype strains with evidence of epidemiological linkage and distinct clusters. Moreover, four major differences were found within the amino acid sequences of BC-loop in VP1 of CV-B strains. In conclusion, this study presented the molecular evolutionary genetic overview and distinct phylogenetic pattern of CV-B isolates from AFP cases in Pakistan, and explored the possible link between CV-B infections and AFP cases. Furthermore, our data reveal that these viruses might contribute to the incidence of paralysis in population and there is need of time to establish an enterovirus surveillance system for better understanding of epidemiological and virological characteristics of NPEV infections associated with AFP cases in the country.
Topics: Capsid Proteins; Child; Child, Preschool; Coxsackievirus Infections; Disease Eradication; Enterovirus B, Human; Feces; Female; Humans; Infant; Male; Pakistan; Paralysis; Phylogeny; Poliomyelitis; Sequence Analysis, RNA
PubMed: 28738914
DOI: 10.1017/S0950268817001522