Influence of the Theiler's virus L* protein on macrophage infection, viralpersistence, and neurovirulence

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.