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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 5
pubmed:dateCreated
2005-4-15
pubmed:databankReference
pubmed:abstractText
Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease and is sometimes associated with serious neurological disorders. In this study, an attempt was made to identify molecular determinants of EV71 attenuation of neurovirulence in a monkey infection model. An infectious cDNA clone of the virulent strain of EV71 prototype BrCr was constructed; temperature-sensitive (ts) mutations of an attenuated strain of EV71 or of poliovirus (PV) Sabin vaccine strains were then introduced into the infectious clone. In vitro and in vivo phenotypes of the parental and mutant viruses were analysed in cultured cells and in cynomolgus monkeys, respectively. Mutations in 3D polymerase (3D(pol)) and in the 3' non-translated region (NTR), corresponding to ts determinants of Sabin 1, conferred distinct temperature sensitivity to EV71. An EV71 mutant [EV71(S1-3')] carrying mutations in the 5' NTR, 3D(pol) and in the 3' NTR showed attenuated neurovirulence, resulting in limited spread of virus in the central nervous system of monkeys. These results indicate that EV71 and PV1 share common genetic determinants of neurovirulence in monkeys, despite the distinct properties in their original pathogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1317
pubmed:author
pubmed:issnType
Print
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1391-401
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15831951-3' Untranslated Regions, pubmed-meshheading:15831951-5' Untranslated Regions, pubmed-meshheading:15831951-Animals, pubmed-meshheading:15831951-Base Sequence, pubmed-meshheading:15831951-Brain, pubmed-meshheading:15831951-Cells, Cultured, pubmed-meshheading:15831951-Central Nervous System Viral Diseases, pubmed-meshheading:15831951-Disease Models, Animal, pubmed-meshheading:15831951-Enterovirus, pubmed-meshheading:15831951-Enterovirus Infections, pubmed-meshheading:15831951-Female, pubmed-meshheading:15831951-Macaca fascicularis, pubmed-meshheading:15831951-Models, Molecular, pubmed-meshheading:15831951-Molecular Sequence Data, pubmed-meshheading:15831951-Nucleic Acid Conformation, pubmed-meshheading:15831951-Poliovirus, pubmed-meshheading:15831951-RNA Replicase, pubmed-meshheading:15831951-Spinal Cord, pubmed-meshheading:15831951-Viral Plaque Assay, pubmed-meshheading:15831951-Virulence
pubmed:year
2005
pubmed:articleTitle
Temperature-sensitive mutants of enterovirus 71 show attenuation in cynomolgus monkeys.
pubmed:affiliation
Department of Virology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't