O. Van Eyll et T. Michiels, Influence of the Theiler's virus L* protein on macrophage infection, viralpersistence, and neurovirulence, J VIROLOGY, 74(19), 2000, pp. 9071-9077
The genome of picornaviruses contains a large open reading frame (ORF) tran
slated as a precursor polypeptide that is processed to yield all the protei
ns necessary for the viral life cycle. In persistent but not in neurovirule
nt strains of Theiler's virus, an overlapping ORF encodes an additional 18-
kDa protein called L*. We confirmed previous work showing that the La ORF o
f persistent strains facilitates the infection of macrophage cell lines, an
d we present evidence that this effect is due to the L* protein itself rath
er than to competition for the translation of the two overlapping ORFs. The
introduction of an AUG codon to restore the L* ORF of the neurovirulent GD
VII strain also enhanced the infection of macrophages, in spite of the dive
rgent evolution of this protein. The presence or the absence of the L* AUG
initiation codon had only a weak influence on the neurovirulence of the GDV
II strain and on the persistence of the DA1 strain. The results obtained wi
th DA1 in vivo contrast,vith the results reported previously for DAFL3, ano
ther molecular clone of the same virus strain, where the AUG-to-ACG mutatio
n of the Lb initiation codon totally blocked viral persistence (G. D. Ghadg
e, L, Ma, S, Sate, J, Kim, and R. P. Roos, J. Virol. 72:8605-8612, 1998), T
hus, a factor that is critical for the persistence of a given clone of Thei
ler's virus is dispensable for the persistence of a closely related clone,
indicating that different adjustments in the expression of persistence dete
rminants occur in related viral strains.