Expression and functional properties of proteins encoded in the x-II ORF of HTLV-I

With the aim of identifying viral proteins that contribute to the distinctive properties of HTLV-I biology and pathogenicity, several laboratories have investigated the coding potential of the X region of the genome, which includes five partially overlapping open reading frames (ORFs). We and others have shown that, in addition to the essential regulatory proteins Rex and Tax, a number of accessory proteins encoded in the X region can be produced by alternative splicing and multicistronic translation. One X region ORF, termed X-II, produces two protein isoforms named Tof/p30 II and p13 II, which are expressed from a doubly- and singly-spliced mRNA, respectively. Initial functional analyses demonstrated that Tof/p30 II is a nucleolar/nuclear protein that possesses a region capable of binding to RNA, and p13 II is a mitochondrial protein that alters the morphology and function of this organelle. Together with data from other laboratories demonstrating the production of antibodies and CTL against x-II ORF products in HTLV-I infected subjects and the requirement of this ORF for efficient viral replication in vivo, these findings suggest that further characterization of Tof/p30 II and p13 II will yield insight into remaining undefined aspects of HTLV-I pathogenicity and replication.