HTLV-1 propels untransformed CD4 lymphocytes into the cell cycle while protecting CD8 cells from death.
Human T cell leukemia virus type 1 (HTLV-1) infects both CD4+ and CD8+ lymphocytes, yet it induces adult T cell leukemia/lymphoma (ATLL) that is regularly of the CD4+ phenotype. Here we show that in vivo infected CD4+ and CD8+ T cells displayed similar patterns of clonal expansion in carriers without malignancy. Cloned infected cells from individuals without malignancy had a dramatic increase in spontaneous proliferation, which predominated in CD8+ lymphocytes and depended on the amount of tax mRNA. In fact, the clonal expansion of HTLV-1-positive CD8+ and CD4+ lymphocytes relied on 2 distinct mechanisms--infection prevented cell death in the former while recruiting the latter into the cell cycle. Cell cycling, but not apoptosis, depended on the level of viral-encoded tax expression. Infected tax-expressing CD4+ lymphocytes accumulated cellular defects characteristic of genetic instability. Therefore, HTLV-1 infection establishes a preleukemic phenotype that is restricted to CD4+ infected clones.
Sibon
David
D
Oncovirologie et Biothérapies, CNRS UMR5537- Université Claude Bernard, Centre Léon Bérard, Lyon, France.
Gabet
Anne-Sophie
AS
Zandecki
Marc
M
Pinatel
Christiane
C
Thête
Julien
J
Delfau-Larue
Marie-Hélène
MH
Rabaaoui
Samira
S
Gessain
Antoine
A
Gout
Olivier
O
Jacobson
Steven
S
Mortreux
Franck
F
Wattel
Eric
E
D000328:Adult; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002353:Carrier State / Q000821:virology; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011289:Preleukemia / Q000378:metabolism / Q000821:virology; D013997:Time Factors