{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:31:22Z","timestamp":1791235882333,"version":"4.1.0"},"reference-count":73,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2008,2,15]],"date-time":"2008-02-15T00:00:00Z","timestamp":1203033600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2008,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also associated with serious neurological disorders. An attenuated EV71 strain [EV71(S1-3\u2032)] has been established in the cynomolgus monkey infection model; this strain contains the attenuation determinants derived from the type 1 poliovirus vaccine strain, Sabin 1 [PV1(Sabin)], in the 5\u2032 nontranslated region (NTR), 3D polymerase, and 3\u2032 NTR. In this study, we analyzed the effect of the attenuation determinants of PV1(Sabin) on EV71 infection in a NOD\/SCID mouse infection model. We isolated a mouse-adapted EV71 strain [EV71(NOD\/SCID)] that causes paralysis of the hind limbs in 3- to 4-week-old NOD\/SCID mice by adaptation of the virulent EV71(Nagoya) strain in the brains of NOD\/SCID mice. A single mutation at nucleotide 2876 that caused an amino acid change in capsid protein VP1 (change of the glycine at position 145 to glutamic acid) was essential for the mouse-adapted phenotype in NOD\/SCID mice. Next, we introduced attenuation determinants derived from PV1(Sabin) along with the mouse adaptation mutation into the EV71(Nagoya) genome. In 4-week-old mice, the determinants in the 3D polymerase and 3\u2032 NTR, which are the major temperature-sensitive determinants, had a strong effect on attenuation. In contrast, the effect of individual determinants was weak in 3-week-old NOD\/SCID mice, and all the determinants were required for substantial attenuation. These results suggest that a cooperative effect of the attenuation determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71.<\/jats:p>","DOI":"10.1128\/jvi.01798-07","type":"journal-article","created":{"date-parts":[[2007,12,6]],"date-time":"2007-12-06T02:00:33Z","timestamp":1196906433000},"page":"1787-1797","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":98,"title":["Cooperative Effect of the Attenuation Determinants Derived from Poliovirus Sabin 1 Strain Is Essential for Attenuation of Enterovirus 71 in the NOD\/SCID Mouse Infection Model"],"prefix":"10.1128","volume":"82","author":[{"given":"Minetaro","family":"Arita","sequence":"first","affiliation":[{"name":"Department of Virology II"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Ami","sequence":"additional","affiliation":[{"name":"Division of Experimental Animals Research, National Institute of 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