Clonal expansion of HTLV-1 infected cells depends on the CD4 versus CD8 phenotype.
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.
Zane
Linda
L
Oncovirology and Biotherapy, FRE CNRS 3011 Lyon I University, Leon Berard Center, Lyon France.
Sibon
David
D
Mortreux
Franck
F
Wattel
Eric
E
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology; D014644:Genetic Variation; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000821:virology; D015493:Paraparesis, Tropical Spastic / Q000097:blood / Q000821:virology; D014779:Virus Replication