RT Journal Article SR Electronic(1) A1 Arita, Minetaro A1 Shimizu, Hiroyuki A1 Nagata, Noriyo A1 Ami, Yasushi A1 Suzaki, Yuriko A1 Sata, Tetsutaro A1 Iwasaki, Takuya A1 Miyamura, TatsuoYR 2005 T1 Temperature-sensitive mutants of enterovirus 71 show attenuation in cynomolgus monkeys JF Journal of General Virology, VO 86 IS 5 SP 1391 OP 1401 DO https://doi.org/10.1099/vir.0.80784-0 PB Microbiology Society, SN 1465-2099, AB 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 (3Dpol) 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, 3Dpol 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.80784-0