Attenuation of neurovirulence of Theiler's murine encephalomyelitis virus strain GDVII is not sufficient to establish persistence in the central nervous system.
Virus recombinants constructed from Theiler's murine encephalomyelitis virus (TMEV) strain GDVII, which causes a rapidly fatal encephalitis in mice, and the less virulent BeAn, which persists in the murine central nervous system (CNS) and causes inflammatory demyelination, and a GDVII mutant deleted of 46 of 76 leader protein amino acids were analysed for virus persistence in the CNS. The two recombinant and mutant viruses principally contain GDVII sequences including the nucleotides encoding the polyprotein and 3' untranslated region. These viruses were found to replicate in the CNS of mice but they did not produce acute encephalitis or paralysis, i.e. they were attenuated in neurovirulence compared to the GDVII parent. More important, none of the viruses persisted in the mouse CNS nor caused chronic demyelination. Thus, attenuation of GDVII neurovirulence alone is not sufficient to establish TMEV persistence. This result is discussed in the context of a genomic determinant for persistence.
Lipton
H L
HL
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston Hospital, IL 60201, USA. hllipton@merle.acns.nwu.edu
Pritchard
A E
AE
Calenoff
M A
MA
D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000821:virology*; D006224:Cricetinae; D051379:Mice; D011051:Poliomyelitis / Q000821:virology*; D017384:Sequence Deletion; D017945:Theilovirus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D014774:Virulence; D017735:Virus Latency