Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
STUDIES ON THE MECHANISMS OF HTLV-I LEUKEMOGENESIS (MEETING ABSTRACT)
Fifteenth Symposium of the International Association for Comparative Research on Leukemia and Related Diseases. October 6-11, 1991, Padova/Venice, Italy, p. 82, 1991.. Unique Identifier : AIDSLINE ICDB/92682422 Saggioro D; Forino M; Chieco-Bianchi L; Inst. of Oncology, Univ. of Padova, Padova, Italy
Abstract:
Human T-lymphotropic virus type I (HTLV-I) gene expression in vivo and in vitro is quite restricted, even if HTLV-I LTR promoter/enhancer sequences are susceptible to different cellular and viral stimuli. The mechanisms of viral latency remain to be elucidated, but it is believed that host cellular factors are involved. Much evidence supports the notion that methylation may play a role in blocking the transcription of endogenous, as well as exogenous, genes. This inhibition conceivably comes about by preventing specific transcriptional factor from binding to its target sequences on DNA. In studying whether the presence of methyl moieties at the LTR level could inhibit LTR transactivation mediated by both tax and/or PMA, we found that the block was overcome when the two activators were added together in cell culture. These results suggested that methylation might be involved in HTLV-I transcriptional regulation, and that different cellular proteins were involved in tax- or PMA-stimulated LTR activation. Tax protein, besides its transactivating capacity, was also reported to downregulate beta-polymerase gene expression; thus, it is possible that HTLV-I transformation is facilitated by the resulting reduced capacity of DNA repair. ATL cell chromosomal instability has been described; we previously observed that HTLV-I-immortalized T lymphocytes exhibit increased chromosomal aberrations, but the presence of full-length provirus sequences in the host cells hampered understanding of the virus-mediated mechanisms of DNA damage. In more recent experiments, using MOLT-3 lymphoma cells transiently transfected with a tax-expressing plasmid, we studied the frequency of basal- and chemically induced chromosomal aberrations, in terms of induced micronuclei. The results indicated that the micronucleus frequency was higher in cells transfected with tax-expressing plasmid, compared with control cells nontransfected or transfected with a tax-unrelated plasmid. The presence of tax protein also significantly increased the clastogenic effect of chemical carcinogens, indicating that tax product, directly or indirectly, makes the cells more susceptible to DNA damage. HTLV-I transformation thus seems the result of complex interactions between viral and cellular genes; viral products might be needed only to initiate the cascade of events ultimately leading to complete transformation.
Keywords: Chromosome Aberrations DNA Damage DNA Repair Gene Expression Gene Products, tax/GENETICS HIV Long Terminal Repeat/GENETICS HTLV-I/*GENETICS HTLV-I Infections/COMPLICATIONS/*GENETICS Leukemia/*GENETICS Lymphoma/*GENETICS Methylation Plasmids Transcription, Genetic ABSTRACT 920830
M9281100
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
