Evidence for the Chronic in Vivo Production of Human T Cell Leukemia Virus Type I Rof and Tof Proteins from Cytotoxic T Lymphocytes Directed against Viral Peptides

Abstract

Human T cell leukemia virus type I (HTLV-I) is a persistent virus that causes adult T cell leukemia and tropical spastic paraparesis/HTLV-I–associated myelopathy. Studies on rabbits have shown that viral proteins encoded by the open reading frames pX-I and pX-II are required for the establishment of the persistent infection. To examine the in vivo production of these proteins in humans, we have investigated whether cytotoxic T lymphocytes isolated from HTLV-I–infected individuals recognized pX-I and pX-II peptides. CD8+ T lymphocytes to pX-I and pX-II peptides were detected in HTLV-I–infected individuals, whatever their clinical status, and even in the absence of any antigenic restimulation. These findings indicate that the HTLV-I pX-I and pX-II proteins are chronically synthesized in vivo, and are targets of the natural immune response to the virus.

Mitochondrial Alterations Induced by the p13II Protein of Human T-cell Leukemia Virus Type 1

“…Expression of p13 II results in specific alterations in mitochondrial morphology and distribution from an extensively intercon-nected network of string-like structures to clusters of spheroid bodies, suggesting that p13 II might interfere with mitochondrial function in situ (13). This observation along with the findings that the p13 II -coding sequence is conserved among HTLV-1 isolates, that its mRNA is expressed during HTLV-1 infection and disease (5,14), and that cytotoxic T-lymphocytes against the x-II ORF are detected in HTLV-1-infected individuals (12) indicate that the protein might exert a significant biological role in viral replication and/or pathogenesis. The present study was undertaken to unravel the function of p13 II through (i) determination of its submitochondrial localization and sequences required to induce the alterations in mitochondrial morphology and (ii) an assessment of the biophysical and biological properties of a set of synthetic peptides spanning residues 9 -41, which include the amphipathic MTS of the protein.…”

“…Although the accessory ORFs are dispensable for virus propagation and immortalization of T-cells in vitro (6 -8), they are essential for efficient viral propagation in animal models (9 -11). In addition, cell-mediated immune responses against these gene products have been demonstrated in infected individuals (12), thus providing strong evidence that these proteins are expressed during the natural history of HTLV-1 infection.…”

Molecular and cellular aspects of HTLV-1 associated leukemogenesis in vivo

“…68,69 In humans, circulating specific pX-I and pX-II CD8 + T lymphocytes are regularly observed, whatever the clinical status. 70 This indicates that pX-I and pX-II are synthesized in vivo. Recent works have demonstrated that by activating nuclear factor of activated T cells, p12 I is critical for viral infectivity in quiescent primary lymphocytes.…”

Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR

“…Furthermore, p12 appears to be preferentially expressed over p27. Although there is evidence that p27 is expressed in vivo (Pique et al, 2000) and in vitro (Ciminale et al, 1992), the precise function of p27 in HTLV-1 replication remains unclear.…”