With the aim of identifying viral proteins that contribute to the distincti
ve properties of HTLV-1 biology and pathogenicity, several laboratories hav
e investigated the coding potential of the X region of the genome, which in
cludes 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), w
hich are expressed from a doubly- and singly-spliced mRNA, respectively. In
itial functional analyses demonstrated that Tof/p30(II) is a nucleolar/nucl
ear 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 pro
duction of antibodies and CTL against x-II ORF products in HTLV-1 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-1 p
athogenicity and replication. (C) 2001 Elsevier Science B.V. All rights res
erved.