High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis.
Adult T cell leukemia (ATLL) develops in 3 - 5% of HTLV-1 carriers after a long period of latency during which a persistent polyclonal expansion of HTLV-1 infected lymphocytes is observed in all individuals. This incubation period is significantly shortened in HTLV-1 carrier with Strongyloides stercoralis (Ss) infection, suggesting that Ss could be a cofactor of ATLL. As an increased T cell proliferation at the asymptomatic stage of HTLV-1 infection could increase the risk of malignant transformation, the effect of Ss infection on infected T lymphocytes was assessed in vivo in HTLV-1 asymptomatic carriers. After real-time quantitative PCR, the mean circulating HTLV-1 proviral load was more than five times higher in HTLV-1 carriers with strongyloidiasis than in HTLV-1+ individuals without Ss infection (P<0.009). This increased proviral load was found to result from the extensive proliferation of a restricted number of infected clones, i.e. from oligoclonal expansion, as evidenced by the semiquantitative amplification of HTLV-1 flanking sequences. The positive effect of Ss on clonal expansion was reversible under effective treatment of strongyloidiasis in one patient with parasitological cure whereas no significant modification of the HTLV-1 replication pattern was observed in an additional case with strongyloidiasis treatment failure. Therefore, Ss stimulates the oligoclonal proliferation of HTLV-1 infected cells in HTLV-1 asymptomatic carriers in vivo. This is thought to account for the shortened period of latency observed in ATLL patients with strongyloidiasis. Oncogene (2000) 19, 4954 - 4960
Gabet
A S
AS
Unité d'Oncogenèse Virale, UMR5537 CNRS-Université Claude Bernard, Centre Léon Bérard, 28 rue Laënnec 69373, Lyon Cedex 08, France.
Mortreux
F
F
Talarmin
A
A
Plumelle
Y
Y
Leclercq
I
I
Leroy
A
A
Gessain
A
A
Clity
E
E
Joubert
M
M
Wattel
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000969:Antinematodal Agents / Q000627:therapeutic use; D002353:Carrier State / Q000097:blood / Q000821:virology; D002648:Child; D002999:Clone Cells; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics / Q000502:physiology*; D017171:Strongyloides stercoralis; D013322:Strongyloidiasis / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology*; D013827:Thiabendazole / Q000627:therapeutic use; D019562:Viral Load; D014779:Virus Replication
D000969:Antinematodal Agents; D013827:Thiabendazole