Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enterovirus 71 (EV71) is a highly infectious major causative agent of hand, foot, and mouth disease (HFMD) which could lead to severe neurological complications. There is currently no effective therapy against EV71. In this study, RNA interference (RNAi) is employed as a therapeutic approach for specific viral inhibition. Various regions of the EV71 genome were targeted for inhibition by chemically synthesized siRNAs. Transfection of rhabdomyosarcoma (RD) cells with siRNA targeting the 3'UTR, 2C, 3C, or 3D region significantly alleviated cytopathic effects of EV71. The inhibitory effect was dosage-dependent with a corresponding decrease in viral RNA, viral proteins, and plaque formations by EV71. Viral inhibition of siRNA transfected RD cells was still evident after 48 h. In addition, no significant adverse off-target silencing effects were observed. These results demonstrated the potential and feasibility for the use of siRNA as an antiviral therapy for EV71 infections.
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PMID:RNA interference against enterovirus 71 infection. 1608 32

Enterovirus 71 (EV71) causes seasonal epidemics of hand-foot-and-mouth disease associated with fatal neurological complications in young children, and several major outbreaks have occurred recently. This study developed an effective antiviral agent by transforming the gene for VP1 protein, a previously defined epitope and also a coat protein of EV71, into tomato plant. VP1 protein was first fused with sorting signals to enable it to be retained in the endoplasmic reticulum of tomato plant, and its expression level increased to 27 microg/g of fresh tomato fruit. Transgenic tomato fruit expressing VP1 protein was then used as an oral vaccine, and the development of VP1-specific fecal IgA and serum IgG were observed in BALB/c mice. Additionally, serum from mice fed transgenic tomato could neutralize the infection of EV71 to rhabdomyosarcoma cells, indicating that tomato fruit expressing VP1 was successful in orally immunizing mice. Moreover, the proliferation of spleen cells from orally immunized mice was stimulated by VP1 protein, and provided further evidence of both humoral and cellular immunity. Results of this study not only demonstrate the feasibility of using transgenic tomato as an oral vaccine to generate protective immunity in mice against EV71, but also suggest the probability of enterovirus vaccine development.
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PMID:Oral immunization of mice using transgenic tomato fruit expressing VP1 protein from enterovirus 71. 1644 30

Enterovirus 71 (EV71) is the main causative agent of hand, foot, and mouth disease (HFMD) in young children. It has been associated with severe neurological complications and has caused significant mortalities in large-scale outbreaks in Asia. In this study, we demonstrated an enhanced silencing of EV71 through the use of chemically synthesized 29-mer shRNAs. The 29-mer shRNAs were designed to target three highly conserved regions of EV71 genome. Transfection of rhabdomyosarcoma (RD) cells with the 29-mer shRNAs significantly inhibited EV71 replication in a dose-dependent manner as demonstrated by reduction of viral RNA, VP1 protein and plaque forming units. The inhibitory effects were more potent and were achieved at 10-fold lower concentrations when compared to 19-mer siRNAs reported previously [Sim, A.C.N., Luhur, A., Tan, T.M.C., Chow, V.T.K., Poh, C.L., 2005. RNA interference against Enterovirus 71 infection. Virology 341, 72-79]. The viral inhibitory effects lasted 72 h post-infection and there was no adverse off-target silencing effect. Gene silencing by 29-mer shRNAs targeted at the 3D(pol) region (sh-3D) was the most effective, achieving 91% viral inhibition. Further evaluation found that no enhanced inhibitory effects were observed when sh-3D was cotransfected with each of the other two candidates. This study showed an improvement in triggering RNAi using the more potent 29-mer shRNAs, indicating its therapeutic potential against EV71.
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PMID:Enhanced potency and efficacy of 29-mer shRNAs in inhibition of Enterovirus 71. 1731 36

Enterovirus 71 (EV 71) is one of the commonest causative agents of hand, foot, and mouth disease (HFMD), which infects mainly young children. It has been associated with severe neurological complications worldwide, and has caused significant deaths in many provinces of China from March to May 2008. In this study, RNA interference (RNAi) was used as an antiviral agent to inhibit EV 71 replication in rhabdomyosarcoma (RD) cells. Three small interfering RNAs (siRNAs) targeting extremely conserved regions among multiple EV 71 strains in China could effectively block the replication of EV 71 strain Shzh-98. Combination transfection of these three siRNAs could produce a strong inhibitory effect not only in strain Shzh-98, but also in one epidemic strain Fuyang-0805 isolated from a child in the city of Fuyang with a clinical diagnosis of HFMD in 2008. These strategies and results suggest that RNAi has potential therapeutic use for the suppression of EV 71 infection in a broad spectrum of viral strains.
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PMID:Identification of small interfering RNAs which inhibit the replication of several Enterovirus 71 strains in China. 1949 Sep 79

Enterovirus 71 (EV71) is the main etiologic agent of hand, foot, and mouth disease (HFMD) and causes frequently severe neurological complications and mortality in young children. The serum neutralizing antibody response is the major indicator of EV71 infection and protective immunity. The current serum neutralization test based on inhibition of cytopathic effect (Nt-CPE) requires manual microscopic examination, which is time-consuming and labor-intensive. In this study, a high-throughput neutralization assay which employs enzyme immunoassay for detecting growth of EV71 in Rhabdomyosarcoma (RD) cells and measuring serum neutralizing antibody (Nt-EIA) against EV71 was developed. RD cells infected with 100 TCID(50) of EV71 for 36-42h had the best performance and were selected for Nt-EIA. One hundred and twenty human sera (59 negative sera, 61 positive sera) were measured for EV71 neutralization antibody titers by Nt-CPE and Nt-EIA. Neutralization antibody titers against EV71 determined by Nt-EIA had a high sensitivity (100%), specificity (94.9%) and agreement (97.5%) by a qualitative comparison with Nt-CPE. In the quantitative comparison, the correlation coefficient between Nt-EIA and Nt-CPE was 0.91 after log transformation. Overall, the Nt-EIA is a suitable alternative assay for the quantitation of EV71 neutralizing antibody to EV71.
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PMID:Development of a high-throughput assay for measuring serum neutralizing antibody against enterovirus 71. 2003 86

This study aimed to reveal the pathogen spectrum of hand-foot-and-mouth disease (HFMD) and genetic characteristics of Coxsackievirus A16 (CoxA16) isolates in Beijing in 2009. From 1044 clinical specimens collected from 975 HFMD cases at Beijing Pediatrics Hospital, Beijing You'an Hospital and Beijing Ditan Hospital in 2009, viral nucleic acids of enterovirus were detected by reverse transcriptase polymerase chain reaction (RT-PCR). Enterovirus isolations were conducted with rhabdomyosarcoma (RD) cell line on 200 throat swabs having positive RT-PCR results. Sequencing and analyses of VP1 encoding gene were performed on 9 CoxA16 isolates in this study. The results showed that CoxA16 (49.4%) and EV71 (36.4%) were the major pathogens for the epidemics of HFMD in 2009 in Beijing, and CoxA16 was the predominant serotype, while there were also other enterovirus co-circulating, such as CoxA4, CoxA10, and CoxA9; the CoxA16 strains prevalent in Beijing in 2009 belonged to subgenotype B1a and B1b.
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PMID:[Etiology of hand-foot-and-mouth disease and genetic characteristics of Coxsackievirus A16 in Beijing, 2009]. 2134 45

Enterovirus 71 (EV71) infections can usually cause epidemic hand, foot, and mouth disease (HFMD), and occasionally lead to aseptic meningitis, encephalitis, and polio-like illness. Skeletal muscles have been thought to be crucial for the pathogenesis of EV71-related diseases. However, little is known about the virulence of mouse muscle-adapted EV71. The EV71 0805 were subjected to four passages in the mouse muscle to generate a mouse-adapted EV71 strain of 0805a. In comparison with the parental EV71 0805, the mouse muscle-adapted EV71 0805a displayed stronger cytotoxicity against Rhabdomyosarcoma (RD) cells and more efficient replication in RD cells. Furthermore, infection with the EV71 0805a significantly inhibited the gain of body weight, accompanied by increased muscle virus load and multiple tissue distribution in the infected mouse. Histological examinations indicated that infection with the EV71 0805 did not cause obvious pathogenic lesions in mice, while infection with the muscle-adapted 0805a resulted in severe necrotizing myositis in the skeletal and cardio muscles, and intestinitis in mice on day 5 post infection. Further analysis revealed many mutations in different regions of the genome of mouse muscle-adapted virus. Collectively, these data demonstrated the mouse muscle-adapted EV71 0805a with increased virulence in mice.
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PMID:A mouse muscle-adapted enterovirus 71 strain with increased virulence in mice. 2161 64

Outbreaks of hand, foot, and mouth disease caused by enterovirus 71 (EV71) have become considerable threats to the health of infants and young children. To identify the cellular long noncoding RNAs (lncRNAs) involved in the host response to EV71 infection, we performed comprehensive lncRNA and mRNA profiling in EV71-infected rhabdomyosarcoma cells through microarray. We observed the differential expression of more than 4800 lncRNAs during infection. Further analysis showed 160 regulated enhancer-like lncRNA and nearby mRNA pairs, as well as 313 regulated Rinn's lncRNA [M. Guttman I. Amit, M. Garber, C. French, M.F. Lin, D. Feldser, M. Huarte, O. Zuk, B.W. Carey, J.P. Cassady, M.N. Cabili, R. Jaenisch, T.S. Mikkelsen, T. Jacks, N. Hacohen, B.E. Bernstein, M. Kellis, A. Regev, J.L. Rinn, E.S. Lander. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458 (2009) 223-227, A.M. Khalil, M. Guttman, M. Huarte, M. Garber, A. Raj, D. Rivea Morales, K. Thomas, A. Presser, B.E. Bernstein, A. van Oudenaarden, A. Regev, E.S. Lander, J.L. Rinn. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc. Natl. Acad. Sci. USA 106 (2009) 11667-11672] and nearby mRNA pairs. The results provided information for further research on the prevention and treatment of EV71 infection, as well as on distinguishing severe and mild EV71 cases.
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PMID:lncRNA expression signatures in response to enterovirus 71 infection. 2322 Feb 33

Large-scale Hand, Foot, and Mouth Disease (HFMD) outbreaks have frequently occurred in China since 2008, affecting more than one million children and causing several hundred children deaths every year. The pathogens of HFMD are mainly human enteroviruses (HEVs). Among them, human enterovirus 71 (HEV71) and coxsackievirus A16 (CVA16) are the most common pathogens of HFMD. However, other HEVs could also cause HFMD. To rapidly detect HEV71 and CVA16, and ensure detection of all HEVs causing HFMD, two real-time hybridization probe-based RT-PCR assays were developed in this study. One is a multiplex real-time RT-PCR assay, which was developed to detect and differentiate HEV71 specifically from CVA16 directly from clinical specimens within 1-2 h, and the other is a broad-spectrum real-time RT-PCR assay, which targeted almost all HEVs. The experiments confirmed that the two assays have high sensitivity and specificity, and the sensitivity was up to 0.1 TCID50/ml for detection of HEVs, HEV71, and CVA16, respectively. A total of 213 clinical specimens were simultaneously detected by three kinds of assays, including the two real-time RT-PCR assays, direct conventional RT-PCR assay, and virus isolation assay on human rhabdomyosarcoma cells (RD cells). The total positive rate of both HEV71 and CVA16 was 69.48% with real-time RT-PCR assay, 47.42% with RT-PCR assay, and 34.58% with virus isolation assay. One HFMD clinical specimen was positive for HEV, but negative for HEV71 or CVA16, which was identified as Echovirus 11 (Echo11) by virus isolation, RT-PCR, and sequencing for the VP1 gene. The two real-time RT-PCR assays had been applied in 31 provincial HFMD labs to detect the pathogens of HFMD, which has contributed to the rapid identification of the pathogens in the early stages of HFMD outbreaks, and helped to clarify the etiologic agents of HFMD in China.
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PMID:The development and application of the two real-time RT-PCR assays to detect the pathogen of HFMD. 2363 36

Enterovirus 71 (EV71) causes hand, foot, and mouth disease and severe neurological disorders in children. Human scavenger receptor class B member 2 (hSCARB2) and P-selectin glycoprotein ligand-1 (PSGL-1) are identified as receptors for EV71. The underling mechanism of PSGL-1-mediated EV71 entry remains unclear. The endocytosis required for EV71 entry were investigated in Jurkat T and mouse L929 cells constitutively expressing human PSGL-1 (PSGL-1-L929) or human rhabdomyosarcoma (RD) cells displaying high SCARB2 but no PSGL-1 by treatment of specific inhibitors or siRNA. We found that disruption of clathrin-dependent endocytosis prevented EV71 infection in RD cells, while there was no influence in Jurkat T and PSGL-1-L929 cells. Disturbing caveolar endocytosis by specific inhibitor or caveolin-1 siRNA in Jurkat T and PSGL-1-L929 cells significantly blocked EV71 infection, whereas it had no effect on EV71 infection in RD cells. Confocal immunofluorescence demonstrated caveola, and EV71 was directly colocalized. pH-dependent endosomal acidification and intact membrane cholesterol were important for EV71 infection, as judged by the pretreatment of inhibitors that abrogated the infection. A receptor-dominated endocytosis of EV71 infection was observed: PSGL-1 initiates caveola-dependent endocytosis and hSCARB2 activates clathrin-dependent endocytosis.
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PMID:Caveolar endocytosis is required for human PSGL-1-mediated enterovirus 71 infection. 2376 Feb 34


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