10A1-MuLV but not the related amphotropic 4070A MuLV is highly neurovirulent: importance of sequences upstream of the structural Gag coding region.
Recombinants of Moloney murine leukemia virus (MoMuLV) with either an amphotropic (MoAmphoV) or 10A1-tropic host range (Mo10A1V) induce a spongiform neurodegenerative disease in susceptible mice. To test whether MoMuLV -derived sequences are required for induction of neuropathology, mice were inoculated with either the original 10A1 or the amphotropic (4070A) MuLV isolate. Strikingly, wild-type 10A1 was more neurovirulent than Mo10A1V, inducing severe neurological clinical symptoms with a median latency of 99 days in 100% of infected mice. In contrast, no motor disturbances were detected in any of the 4070A-infected mice, although limited central nervous system lesions were observed. A viral determinant conferring high neurovirulence to 10A1 was mapped to a region encompassing the first 676 bases of the viral genome, including the U5 LTR and encoding the amino-terminus of glycosylated Gag (glycoGag). In contrast to studies with the highly neurovirulent CasFr(KP) virus, an inverse correlation between surface expression levels of glycoGag and neurovirulence was not observed; however, this does not rule out a common underlying mechanism regulating virus pathogenicity.
Münk
Carsten
C
Department of Cell and Virus Genetics, Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, D-20251 Hamburg, Germany.
Prassolov
Vladimir
V
Rodenburg
Michaela
M
Kalinin
Viacheslav
V
Löhler
Jürgen
J
Stocking
Carol
C
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002531:Cerebellum / Q000473:pathology; D015750:Genes, gag; D016679:Genome, Viral; D051379:Mice; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics* / Q000472:pathogenicity; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000821:virology*; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D014758:Viral Core Proteins; D014774:Virulence / Q000235:genetics*; D017735:Virus Latency
D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D014758:Viral Core Proteins