Theiler's virus L* protein is targeted to the mitochondrial outer membrane

The L* protein encoded by Theiler's murine encephalomyelitis virus (TMEV) is a unique example of a picornaviral protein encoded by an alternative open reading frame. This protein is an important determinant of TMEV persistence in the mouse central nervous system. We showed that in infected cells, L* is partitioned between the cytosol and the mitochondria. In mitochondria, L* is anchored in the outer membrane and exposed to the cytosol. The targeting of L* to mitochondria is independent of other viral components and likely depends on a conformational signal. L* targeting to mitochondria might involve chaperones of the Hsp70 family, as these proteins are shown to interact.