Abstract:
The role of the human T-cell leukemia virus (HTLV) family in leukemia and immunosuppression and the mechanism of transformation, are discussed. Topics include growth of T-lymphoid cells, isolation and characterization of HTLV-1, epidemiology of HTLV-1 infection, clinical and pathological characteristics of adult T-cell leukemia-lymphoma (ATLL), monoclonality of HTLV-1-induced malignancies, transformation of lymphocytes by HTLV-1 in vitro, the role of T-cell growth factor (TCGF) receptors on HTLV-1-transformed lymphocytes, possible biological functions of the X region, cellular sequences activated in HTLV-transformed cells, HTLV-2, and subhuman primate homologues of HTLV (primate T-cell leukemia virus). HTLV-1 has many of the properties of a chronic leukemia virus, but can also transform T-cells, suggesting that HTLV-1 may accomplish transformation by a novel mechanism. Failure to demonstrate TCGF mRNA in HTLV-1-infected, TCGF-independent cell lines eliminates TCGF as playing a role in transformation, but still does not explain the presence of TCGF receptors on transformed cell lines. A comparison of the HTLV-1 and HTLV-2 genomes by Southern blotting analysis and heteroduplex mapping reveals a 1.O Kb sequence within the X region which appears to be one of the most conserved parts of the genome. Results suggest that a protein product of a long open reading frame within this region may mediate a biological property shared by the two viruses, such as T-cell tropism or transformation. The failure to find c-sis activation in all HTLV-transformed cells would argue that it plays a role in the transformation of some or perhaps no cell lines. However, the unique expression of c-sis in these hemopoietic cells suggests an important function for this gene product in this malignancy. HTLV-1 has a direct role in induction of ATLL, and may have a direct role in other diseases, including the B-cell chronic lymphocytic leukemia found in Jamaica. Viruses should be sought in T-cell malignant disorders such as mycosis fungoides, other non-malignant diseases involving T-cell abnormalities, and a wide range of other neoplastic and non-neoplastic conditions. (143 Refs)
Keywords: Animal Antibodies, Viral/ANALYSIS Cell Transformation, Neoplastic/ANALYSIS Cell Transformation, Viral Cells, Cultured DNA, Viral/ANALYSIS *Genes, Viral Haplorhini Human HTLV-BLV Viruses/*GENETICS/IMMUNOLOGY/ISOLATION & PURIF Leukemia/ANALYSIS/*ETIOLOGY/GENETICS *Oncogenes Papio Receptors, Immunologic/ANALYSIS *Retroviridae Infections RNA, Viral/ANALYSIS T-Lymphocytes MEETING PAPER
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