[Frontiers in Bioscience 14, 3935-3941, January 1, 2009]
Clonal expansion of HTLV-1 infected cells depends on the CD4 versus CD8 phenotype

Linda Zane1, David Sibon1, Franck Mortreux1, Eric Wattel1, 2

1Oncovirology and Biotherapy, FRE CNRS 3011 Lyon I University, Leon Berard Center, Lyon France, 2Hematology department, Edouard Herriot University Hospital, Lyon, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. CD4+ and CD8+ T lymphocytes are the major HTLV-1 reservoir
4. Clonal expansion of HTLV-1 infected T cells
5. Proviral genetic variability parallels clonal expansion
6. Pathogenical and clinical implications in ATLL
7. Pathogenical and clinical implications in TSP/HAM
8. Which mechanisms underlie clonal expansion?
9. Molecular causes underlying clonal expansion in vivo
10. References

1. ABSTRACT

As other deltaretroviruses HTLV-1 replication in vivo includes a first short step of reverse transcription that is followed by the persistent clonal expansion of infected cells. In vivo these cells include the CD4+ and CD8+ lymphocytes yet the virus induces adult T cell leukemia/lymphoma (ATLL) that is regularly of the CD4+ phenotype. Cloned infected cells from individuals without malignancy possess a dramatic increase in spontaneous proliferation, which predominated with CD8+ lymphocytes and depends on the amount of tax mRNA. In fact, the clonal expansion of HTLV-1 positive CD8+ and CD4+ lymphocytes relies on two distinct mechanisms: infection prevented cell death in the former whereas recruiting the latter into the cell cycle. Furthermore infected tax-expressing CD4+ lymphocytes cumulate cellular defects characteristic of genetic instability. Therefore, HTLV-1 infection establishes a preleukemic phenotype that is restricted to CD4+ infected clones. Investigating the mechanisms underlying apoptosis, cell cycling and DNA repair in cloned cells from naturally infected individuals will permit to deciphering the molecular pathogenesis of HTLV-1 infection.