Mitochondrial targeting of the p13(II) protein coded by the x-II ORF of human T-cell leukemia/lymphotropic virus type I (HTLV-I)

The X region of the HTLV-I genome contains four major open reading frames ( ORFs), two of which, termed x-I and x-II, are of still undefined biological significance. By indirect immunofluorescence and dual labeling with marker proteins, we demonstrate that p13(II), an 87-amino acid protein coded by t he x-II ORF, is selectively targeted to mitochondria, Mutational analysis r evealed that mitochondrial targeting of p13(II) is directed by an atypical 10-amino acid signal sequence that is not cleaved upon import and is able t o target the Green Fluorescent Protein to mitochondria, Expression of p13(I I) results in specific alterations of mitochondrial morphology and distribu tion from a typical string-like, dispersed network to round-shaped clusters , suggesting that p13(II) might interfere with processes relying on an inta ct mitochondrial architecture. Functional studies of mitochondria with the cationic fluorochrome tetramethylrhodamine revealed that a subpopulation of the cells with p13(II)-positive mitochondria show a disruption in the mito chondrial inner membrane potential (Delta psi), an early event observed in cells committed to apoptosis, Taken together, these results suggest novel v irus-cell interactions that might be important in HTLV-I replication and/or pathogenicity.