Human enterovirus 71(HEV71) is the cause of hand,foot and mouth disease and associated neurological complications in children under five years of age.There has been an increase in HEV71 epidemic activity throughout th...Human enterovirus 71(HEV71) is the cause of hand,foot and mouth disease and associated neurological complications in children under five years of age.There has been an increase in HEV71 epidemic activity throughout the Asia-Pacific region in the past decade,and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. To date there is no effective antiviral treatment and no vaccine is available to prevent HEV71 infection. The increase in prevalence, virulence and geographic spread of HEV71 infection over the past decade provides increasing incentive for the development of new therapeutic and prevention strategies against this emerging viral infection. The current review focuses on the potential, advantages and disadvantages of these strategies. Since the explosion of outbreaks leading to large epidemics in China, research in natural therapeutic products has identified several groups of compounds with anti-HEV71 activities. Concurrently, the search for effective synthetic antivirals has produced promising results. Other therapeutic strategies including immunotherapy and the use of oligonucleotides have also been explored. A sound prevention strategy is crucial in order to control the spread of HEV71. To this end the ultimate goal is the rapid development, regulatory approval and widespread implementation of a safe and effective vaccine. The various forms of HEV71 vaccine designs are highlighted in this review. Given the rapid progress of research in this area, eradication of the virus is likely to be achieved.展开更多
BACKGROUND Acute flaccid paralysis(AFP)and neurogenic respiratory failure rarely occur in children.At the end of 2018,some children with such symptoms were admitted to our hospital.In this study,we aimed to assess two...BACKGROUND Acute flaccid paralysis(AFP)and neurogenic respiratory failure rarely occur in children.At the end of 2018,some children with such symptoms were admitted to our hospital.In this study,we aimed to assess two children with AFP and neurogenic respiratory failure associated with enterovirus D68(EV-D68).CASE SUMMARY Two children admitted to our hospital presented with symptoms and imaging results different from those of acute disseminated encephalomyelitis and hand,foot,and mouth disease.Their main symptoms were AFP and neurogenic respiratory failure.Magnetic resonance imaging showed severe inflammatory injury mainly to the anterior horn cells of the spinal cord.Blood and cerebrospinal fluid samples were collected to assess for pathogens,including bacteria,tuberculosis,cryptococcus,herpes virus,and coxsackie virus,and the results were negative.At the beginning,the two cases were not assessed for EV-D68 in the nasopharyngeal,blood,and cerebrospinal fluid specimens.About 2 mo later,EVD68 was detected in the stool sample of one of the cases.The symptom of AFP was caused by injury to the anterior horn cells at levels C5-L5 of the spinal cord,while neurogenic respiratory failure was at levels C3-C5.CONCLUSION We should pay attention to the detection and diagnosis of EV-D68 and make efforts to develop antivirus drugs and vaccines.展开更多
Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the cr...Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.Results:One extremity flaccid was found in four cases(3 with lower limb,1 with upper limb),two limbs flaccid in three cases(2 with lower limbs,1 with upper limbs),and four limbs flaccid in two cases.Spinal MRI studies showed lesion with high signal in T2-weighted images(T2WI) and low signal T1-weighted images(T1WI) in the spinal cord of all nine cases,and the lesions were mainly in bilateral and unilateral anterior hom of cervical spinal cord and spinal cord below thoracic 9(T9) level.In addition,the midbrain,pons, and medulla,which were involved in 3 cases with brainstem encephalitis,demonstrated abnormal signal.Moreover,spinal cord contrast MRI studies showed mild enhancement in corresponding anterior hom of the involved side,and strong enhancement in its ventral root.Conclusions: EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior hom regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiendy show the characteristic pattern and extent of the lesions which correlated well with the clinical features.展开更多
Procalcitonin(PCT),C-reactive protein(CRP),and white blood cell(WBC)have been used as markers of bacterial infection in children for decades.Previous studies have suggested PCT,CRP,WBC,and percentage of neutrophils(%N...Procalcitonin(PCT),C-reactive protein(CRP),and white blood cell(WBC)have been used as markers of bacterial infection in children for decades.Previous studies have suggested PCT,CRP,WBC,and percentage of neutrophils(%N)may be useful in detecting bacterial infection in children[1-4].However,elevated levels of these biomarkers have also been noted in children with enterovirus infection[5-7].In a study involving 5692 hospitalized children with herpangina or hand,foot,and mouth disease(HFMD)in two periods of years,the medians of CRP were 50.1 and 42.5 mg/L,respectively.展开更多
The Enterovirus 71(EV71)VP4 is co-translationally linked to myristic acid at its amino-terminal glycine residue.However,the role of this myristoylation in the EV71 life cycle remains largely unknown.To investigate thi...The Enterovirus 71(EV71)VP4 is co-translationally linked to myristic acid at its amino-terminal glycine residue.However,the role of this myristoylation in the EV71 life cycle remains largely unknown.To investigate this issue,we developed a myristoylation-deficient virus and reporter(luciferase)pseudovirus with a Gly-to-Ala mutation(G2A)on EV71 VP4.When transfecting the EV71-G2 A genome encoding plasmid in cells,the loss of myristoylation on VP4 did not affect the expression of viral proteins and the virus morphology,however,it did significantly influence viral infectivity.Further,in myristoylation-deficient reporter pseudovirus-infected cells,the luciferase activity and viral genome RNA decreased significantly as compared to that of wild type virus;however,cytopathic effect and viral capsid proteins were not detected in myristoylation-deficient virus-infected cells.Also,although myristoylation-deficient viral RNA and proteins were detected in the second blind passage of infection,they were much fewer in number compared to that of the wild type virus.The replication of genomic RNA and negative-strand viral RNA were both blocked in myristoylation-deficient viruses,suggesting that myristoylation affects viral genome RNA release from capsid to cytoplasm.Besides,loss of myristoylation on VP4 altered the distribution of VP4-green fluorescent protein protein,which disappeared from the membrane structure fraction.Finally,a liposome leakage assay showed that EV71 myristoylation mediates the permeability of the model membrane.Hence,the amino-terminal myristoylation of VP4 is pivotal to EV71 infection and capsidmembrane structure interaction.This study provides novel molecular mechanisms regarding EV71 infection and potential molecular targets for antiviral drug design.展开更多
文摘Human enterovirus 71(HEV71) is the cause of hand,foot and mouth disease and associated neurological complications in children under five years of age.There has been an increase in HEV71 epidemic activity throughout the Asia-Pacific region in the past decade,and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. To date there is no effective antiviral treatment and no vaccine is available to prevent HEV71 infection. The increase in prevalence, virulence and geographic spread of HEV71 infection over the past decade provides increasing incentive for the development of new therapeutic and prevention strategies against this emerging viral infection. The current review focuses on the potential, advantages and disadvantages of these strategies. Since the explosion of outbreaks leading to large epidemics in China, research in natural therapeutic products has identified several groups of compounds with anti-HEV71 activities. Concurrently, the search for effective synthetic antivirals has produced promising results. Other therapeutic strategies including immunotherapy and the use of oligonucleotides have also been explored. A sound prevention strategy is crucial in order to control the spread of HEV71. To this end the ultimate goal is the rapid development, regulatory approval and widespread implementation of a safe and effective vaccine. The various forms of HEV71 vaccine designs are highlighted in this review. Given the rapid progress of research in this area, eradication of the virus is likely to be achieved.
文摘BACKGROUND Acute flaccid paralysis(AFP)and neurogenic respiratory failure rarely occur in children.At the end of 2018,some children with such symptoms were admitted to our hospital.In this study,we aimed to assess two children with AFP and neurogenic respiratory failure associated with enterovirus D68(EV-D68).CASE SUMMARY Two children admitted to our hospital presented with symptoms and imaging results different from those of acute disseminated encephalomyelitis and hand,foot,and mouth disease.Their main symptoms were AFP and neurogenic respiratory failure.Magnetic resonance imaging showed severe inflammatory injury mainly to the anterior horn cells of the spinal cord.Blood and cerebrospinal fluid samples were collected to assess for pathogens,including bacteria,tuberculosis,cryptococcus,herpes virus,and coxsackie virus,and the results were negative.At the beginning,the two cases were not assessed for EV-D68 in the nasopharyngeal,blood,and cerebrospinal fluid specimens.About 2 mo later,EVD68 was detected in the stool sample of one of the cases.The symptom of AFP was caused by injury to the anterior horn cells at levels C5-L5 of the spinal cord,while neurogenic respiratory failure was at levels C3-C5.CONCLUSION We should pay attention to the detection and diagnosis of EV-D68 and make efforts to develop antivirus drugs and vaccines.
基金funded by the Hainan Natural Science Foundation 310119Haiman Health Institution Project(No 2011-22)
文摘Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.Results:One extremity flaccid was found in four cases(3 with lower limb,1 with upper limb),two limbs flaccid in three cases(2 with lower limbs,1 with upper limbs),and four limbs flaccid in two cases.Spinal MRI studies showed lesion with high signal in T2-weighted images(T2WI) and low signal T1-weighted images(T1WI) in the spinal cord of all nine cases,and the lesions were mainly in bilateral and unilateral anterior hom of cervical spinal cord and spinal cord below thoracic 9(T9) level.In addition,the midbrain,pons, and medulla,which were involved in 3 cases with brainstem encephalitis,demonstrated abnormal signal.Moreover,spinal cord contrast MRI studies showed mild enhancement in corresponding anterior hom of the involved side,and strong enhancement in its ventral root.Conclusions: EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior hom regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiendy show the characteristic pattern and extent of the lesions which correlated well with the clinical features.
基金This work was supported by Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties[SZGSP012]Project of the Expert Committee on Clinical Application and Drug Resistance Evaluation of Antimicrobial Drugs of the National Health Commission(KJYWZWH-OT-02-2021-01).
文摘Procalcitonin(PCT),C-reactive protein(CRP),and white blood cell(WBC)have been used as markers of bacterial infection in children for decades.Previous studies have suggested PCT,CRP,WBC,and percentage of neutrophils(%N)may be useful in detecting bacterial infection in children[1-4].However,elevated levels of these biomarkers have also been noted in children with enterovirus infection[5-7].In a study involving 5692 hospitalized children with herpangina or hand,foot,and mouth disease(HFMD)in two periods of years,the medians of CRP were 50.1 and 42.5 mg/L,respectively.
基金supported by the National Natural Science Foundation of China(Grant No.31770184)
文摘The Enterovirus 71(EV71)VP4 is co-translationally linked to myristic acid at its amino-terminal glycine residue.However,the role of this myristoylation in the EV71 life cycle remains largely unknown.To investigate this issue,we developed a myristoylation-deficient virus and reporter(luciferase)pseudovirus with a Gly-to-Ala mutation(G2A)on EV71 VP4.When transfecting the EV71-G2 A genome encoding plasmid in cells,the loss of myristoylation on VP4 did not affect the expression of viral proteins and the virus morphology,however,it did significantly influence viral infectivity.Further,in myristoylation-deficient reporter pseudovirus-infected cells,the luciferase activity and viral genome RNA decreased significantly as compared to that of wild type virus;however,cytopathic effect and viral capsid proteins were not detected in myristoylation-deficient virus-infected cells.Also,although myristoylation-deficient viral RNA and proteins were detected in the second blind passage of infection,they were much fewer in number compared to that of the wild type virus.The replication of genomic RNA and negative-strand viral RNA were both blocked in myristoylation-deficient viruses,suggesting that myristoylation affects viral genome RNA release from capsid to cytoplasm.Besides,loss of myristoylation on VP4 altered the distribution of VP4-green fluorescent protein protein,which disappeared from the membrane structure fraction.Finally,a liposome leakage assay showed that EV71 myristoylation mediates the permeability of the model membrane.Hence,the amino-terminal myristoylation of VP4 is pivotal to EV71 infection and capsidmembrane structure interaction.This study provides novel molecular mechanisms regarding EV71 infection and potential molecular targets for antiviral drug design.
