- Different microRNA alterations contribute to diverse outcomes following EV71 and CA16 infections: Insights from high-throughput sequencing in rhesus monkey peripheral blood mononuclear cells. [Journal Article]
- IJInt J Biochem Cell Biol 2016 Oct 17; 81(Pt A):20-31
- Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are the predominant pathogens of hand, foot, and mouth disease (HFMD). Although these viruses exhibit genetic homology, the clinical manifestations...
Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are the predominant pathogens of hand, foot, and mouth disease (HFMD). Although these viruses exhibit genetic homology, the clinical manifestations caused by the two viruses have some discrepancies. In addition, the underlying mechanisms leading to these differences remain unclear. microRNAs (miRNAs) participate in numerous biological or pathological processes, including host responses to viral infections. Here, we focused on differences in miRNA expression patterns in rhesus monkey peripheral blood mononuclear cells (PBMCs) infected with EV71 and CA16 at various time points using high-throughput sequencing. The results demonstrated that 106 known and 13 novel miRNAs exhibited significant differences, and 32 key miRNAs among them for target prediction presented opposite trends in the EV71- and CA16-infected samples. GO and pathway analysis of the predicted targets showed enrichment in 14 biological processes, 10 molecular functions, 8 cellular components and 104 pathways. Subsequently, regulatory networks of miRNA-transcription factors, miRNA-predicted targets, miRNA-GOs and miRNA-pathways were constructed to reveal the complex regulatory mechanisms of miRNAs during the infection phase. Ultimately, we analysed hierarchical GO categories of the predicted targets involved in immune system processes, which indicated that the innate and adaptive immunity following EV71 and CA16 infections may be remarkably distinct. In conclusion, this report is the first describing miRNA expression profiles in PBMCs with EV71 and CA16 infections using high-throughput sequencing. Our findings could provide a valuable basis for further studies on the regulatory roles of miRNAs related to the different immune responses caused by EV71 and CA16 infections.
- A novel inactivated enterovirus 71 vaccine can elicit cross-protective immunity against coxsackievirus A16 in mice. [Journal Article]
- VVaccine 2016 Oct 19
- Hand, foot, and mouth disease (HFMD) is a highly contagious disease that mainly affects infants and children. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the major pathogens of HFMD. Two ...
Hand, foot, and mouth disease (HFMD) is a highly contagious disease that mainly affects infants and children. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the major pathogens of HFMD. Two EV71 vaccines were recently licensed in China and the administration of the EV71 vaccines is believed to significantly reduce the number of HFMD-related severe or fatal cases. However, a monovalent EV71 vaccine cannot cross-protect against CA16 infection, this may result in that it cannot effectively control the overall HFMD epidemic. In this study, a chimeric EV71, whose VP1/210-225 epitope was replaced by that of CA16, was constructed using a reverse genetics technique to produce a candidate EV71/CA16 bivalent vaccine strain. The chimeric EV71 was infectious and showed similar growth characteristics as its parental strain. The replacement of the VP1/210-225 epitope did not significantly affect the antigenicity and immunogenicity of EV71. More importantly, the chimeric EV71 could induce protective immunity against both EV71 and CA16, and protect neonatal mice against either EV71 or CA16 lethal infections, the chimeric EV71 constructed in this study was shown to be a feasible and promising candidate bivalent vaccine against both EV71 and CA16. The construction of a chimeric enterovirus also provides an alternative platform for broad-spectrum HFMD vaccines development.
- Ambulatory Pediatric Surveillance of Hand, Foot and Mouth Disease as Signal of an Outbreak of Coxsackievirus A6 Infections, France, 2014-2015. [Journal Article]
- EIEmerg Infect Dis 2016; 22(11):1884-1893
- The clinical impact of enteroviruses associated with hand, foot and mouth disease (HFMD) is unknown outside Asia, and the prevalence of enterovirus A71 (EV-A71) in particular might be underestimated....
The clinical impact of enteroviruses associated with hand, foot and mouth disease (HFMD) is unknown outside Asia, and the prevalence of enterovirus A71 (EV-A71) in particular might be underestimated. To investigate the prevalence of enterovirus serotypes and the clinical presentations associated with HFMD in France, we conducted prospective ambulatory clinic-based surveillance of children during April 2014-March 2015. Throat or buccal swabs were collected from children with HFMD and tested for the enterovirus genome. Physical examinations were recorded on a standardized form. An enterovirus infection was detected in 523 (79.3%) of 659 children tested. Two epidemic waves occurred, dominated by coxsackievirus (CV) A6, which was detected in 53.9% of enterovirus-infected children. CV-A6 was more frequently related to atypical HFMD manifestations (eruptions extended to limbs and face). Early awareness and documentation of HFMD outbreaks can be achieved by syndromic surveillance of HFMD by ambulatory pediatricians and rapid enterovirus testing and genotyping.
- The Transcriptome of Rhabdomyosarcoma Cells Infected with Cytolytic and Non-Cytolytic Variants of Coxsackievirus B2 Ohio-1. [Journal Article]
- PlosPLoS One 2016; 11(10):e0164548
- The transcriptomes of cells infected with lytic and non-lytic variants of coxsackievirus B2 Ohio-1 (CVB2O) were analyzed using next generation sequencing. This approach was selected with the purpose ...
The transcriptomes of cells infected with lytic and non-lytic variants of coxsackievirus B2 Ohio-1 (CVB2O) were analyzed using next generation sequencing. This approach was selected with the purpose of elucidating the effects of lytic and non-lytic viruses on host cell transcription. Total RNA was extracted from infected cells and sequenced. The resulting reads were subsequently mapped against the human and CVB2O genomes. The amount of intracellular RNA was measured, indicating lower proportions of human RNA in the cells infected with the lytic virus compared to the non-lytic virus after 48 hours. This may be explained by reduced activity of the cellular transcription/translation machinery in lytic enteroviral replication due to activities of the enteroviral proteases 2A and/or 3C. Furthermore, differential expression in the cells infected with the two virus variants was identified and a number of transcripts were singled out as possible answers to the question of how the viruses interact with the host cells, resulting in lytic or non-lytic infections.
- Ginseng, the natural effectual antiviral: Protective effects of Korean Red Ginseng against viral infection. [Review]
- JGJ Ginseng Res 2016; 40(4):309-314
- Korean Red Ginseng (KRG) is a heat-processed ginseng developed by the repeated steaming and air-drying of fresh ginseng. Compared with fresh ginseng, KRG has been shown to possess greater pharmacolog...
Korean Red Ginseng (KRG) is a heat-processed ginseng developed by the repeated steaming and air-drying of fresh ginseng. Compared with fresh ginseng, KRG has been shown to possess greater pharmacological activities and stability because of changes that occur in its chemical constituents during the steaming process. In addition to anticancer, anti-inflammatory, and immune-modulatory activities, KRG and its purified components have also been shown to possess protective effects against microbial infections. Here, we summarize the current knowledge on the properties of KRG and its components on infections with human pathogenic viruses such as respiratory syncytial virus, rhinovirus, influenza virus, human immunodeficiency virus, human herpes virus, hepatitis virus, norovirus, rotavirus, enterovirus, and coxsackievirus. Additionally, the therapeutic potential of KRG as an antiviral and vaccine adjuvant is discussed.
- Development and evaluation of a rapid recombinase polymerase amplification assay for detection of coxsackievirus A6. [Journal Article]
- AVArch Virol 2016 Oct 8
- Coxsackievirus A6 (CV-A6) is an important pathogen causing hand, foot and mouth disease (HFMD). The aim of this study was to develop and evaluate a rapid real-time reverse transcription recombinase p...
Coxsackievirus A6 (CV-A6) is an important pathogen causing hand, foot and mouth disease (HFMD). The aim of this study was to develop and evaluate a rapid real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for detection of CV-A6. The sensitivity of this assay was 202 copies/reaction, with 100 % specificity. Furthermore, this assay yielded consistent results comparable with a commercial qRT-PCR diagnostic kit. This assay is therefore potentially useful for surveillance of CV-A6 infections and outbreak control.
- Coxsackievirus B heart infections and their putative contribution to sudden unexpected death: An 8-year review of patients and victims in the coastal region of Tunisia. [Journal Article]
- FSForensic Sci Int 2016 Sep 22; 268:73-80
- Coxsackieviruses B (CV B) are known as the most common viral cause of human heart infections. Cardiac inflammations contribute to sudden unexpected death (SUD) significantly. The diagnosis remains di...
Coxsackieviruses B (CV B) are known as the most common viral cause of human heart infections. Cardiac inflammations contribute to sudden unexpected death (SUD) significantly. The diagnosis remains difficult with the traditional diagnostic tests and must be substantially improved. This has prompted health professionals to seek new diagnostic procedures which may provide important clues regarding underlying etiology. The present study is based on patients with infectious heart diseases and SUD victims with no relevant pathologies. They were investigated for possible CV-B infection. Patients with coronary artery diseases and unnatural road and domestic accident victims served as controls. The samples were studied for CV-B applying PCR. Histopathology for inflammatory markers, immunohistochemistry (IHC) for immune inflammatory cells and the enteroviral VP1-capsid protein were performed. Overall, 102 patients and 87 SUD victims were studied. As controls, 100 patients and 54 SUD unnatural accident victims were enrolled. CV-B were detected in 28 patients and 15 SUD victims. The control group samples were completely virus negative. Compared to controls, IHC revealed a significant presence of T and B lymphocytes within the myocardium. Furthermore, enteroviral VP1-capsid protein were detected from samples by IHC. Applying a comprehensive combination of methods, our results demonstrate the involvement of CV-B in cases of heart infection suggesting they play a significant role in SUD. Our results emphasize the importance of opting for a combination of methods.
- Coxsackievirus A16 induced neurological disorders in young gerbils which could serve as a new animal model for vaccine evaluation. [Journal Article]
- SRSci Rep 2016 Sep 26; 6:34299
- Coxsackievirus A16 (CA16) is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD) in the Asia-pacific region. Although CA16 infections are generally mild, severe neur...
Coxsackievirus A16 (CA16) is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD) in the Asia-pacific region. Although CA16 infections are generally mild, severe neurological manifestations or even death has been reported. Studies on CA16 pathogenesis and vaccine development are severely hampered because the small animal models that are currently available show major limitations. In this study, gerbils (Meriones unguiculatus) were investigated for their suitability as an animal model to study CA16 pathogenesis and vaccine development. Our results showed that gerbils up to the age of 21 days were fully susceptible to CA16 and all died within five days post-infection. CA16 showed a tropism towards the skeletal muscle, spinal cord and brainstem of gerbils, and severe lesions, including necrosis, were observed. In addition, an inactivated CA16 whole-virus vaccine administrated to gerbils was able to provide full protection to the gerbils against lethal doses of CA16 strains. These results demonstrate that gerbils are a suitable animal model to study CA16 infection and vaccine development.
- Central nervous system infection following vertical transmission of Coxsackievirus B4 in mice. [Journal Article]
- PDPathog Dis 2016 Sep 20
- Coxsackie B viruses (CV-B) are important pathogens associated with several central nervous system (CNS) disorders. CV-B are mainly transmitted by the faecal-oral route, but there is also evidence for...
Coxsackie B viruses (CV-B) are important pathogens associated with several central nervous system (CNS) disorders. CV-B are mainly transmitted by the faecal-oral route, but there is also evidence for vertical transmission. The outcome of in utero CV-B infections on offspring's CNS is poorly explored. The aim of this study was to investigate vertical transmission of CV-B to the CNS. For this purpose, pregnant Swiss albino mice were intraperitoneally inoculated with CV-B4 E2 at gestational days 10G or 17G. Different CNS compartments were collected and analyzed for virus infection and histopathological changes. Using plaque assays, we demonstrated CV-B4 E2 vertical transmission to offspring's CNS. Viral RNA persisted in the CNS up to 60 days after birth, as evidenced by a sensitive semi-nested(sn) reverse transcripton(RT)-PCR method. This was despite infectious particles becoming undetectable at later time points. Persistence was associated with inflammatory lesions, lymphocyte infiltration and viral dsRNA detected by immunohistochemistry. Offspring born to dams mock- or virus-infected at day 17G were challenged by the same virus at day 21 after birth (-+ and ++ groups, respectively). Sn-RT-PCR and histology results compared between both ++ and -+ groups, show that in utero infection did not enhance CNS infection during challenge of the offspring with the same virus.
New Search Next
- A neonatal mouse model for the evaluation of antibodies and vaccines against coxsackievirus A6. [Journal Article]
- ARAntiviral Res 2016; 134:50-57
- Coxsackievirus A6 (CA6) can induce atypical hand, foot, and mouth disease, which is characterized by severe rash, onychomadesis and a higher rate of infection in adults. Increasing epidemiological da...
Coxsackievirus A6 (CA6) can induce atypical hand, foot, and mouth disease, which is characterized by severe rash, onychomadesis and a higher rate of infection in adults. Increasing epidemiological data indicated that outbreaks of CA6-associated hand, foot, and mouth disease have markedly increased worldwide in recent years. However, the current body of knowledge on the infection, pathogenic mechanism, and immunogenicity of CA6 is still very limited. In this study, we established the first neonatal mouse model for the evaluation of antibodies and vaccines against CA6. The CA6 strain CA6/141 could infect a one-day-old BALB/c mouse through intraperitoneal and intracerebral routes. The infected mice developed clinical symptoms, such as inactivity, wasting, hind-limb paralysis and even death. Pathological examination indicated that CA6 showed special tropism to skeletal muscles and skin, but not to nervous system or cardiac muscles. Infections with CA6 could induce vesicles in the dermis without a rash in mice, and the CA6 antigen was mainly localized in hair follicles. The strong tropism of CA6 to the skin may be related to its severe clinical features in infants. This mouse model was further applied to evaluate the efficacy of a therapeutic antibody and an experimental vaccine against CA6. A potential mAb 1D5 could fully protect mice from a lethal CA6 infection and also showed good therapeutic effects in the CA6-infected mice. In addition, an inactivated CA6 vaccine was evaluated through maternal immunization and showed 100% protection of neonatal mice from lethal CA6 challenge. Collectively, these results indicate that this infection model will be a useful tool in future studies on vaccines and antiviral reagents against CA6.