Retroviruses as etiologic agents of some animal and human leukemias and lymphomas and as tools for elucidating the molecular mechanism of leukemogenesis

Abstract

Retroviruses are etiologic agents of naturally occurring leukemias and lymphomas in several animal species (chickens, wild mice, cats, rats, cows, and gibbon apes). One class of viruses (the acutely transforming viruses) carry transformation-specific genes (onc genes) derived from highly conserved normal cellular genes that may be important in basic cellular functions and/or differentiation. The other class of viruses lack definable onc genes, do not transform cells in vitro, and require long latency periods for disease induction. One mechanism by which retroviruses that lack onc genes induce leukemias may be activation of resident cellular onc genes. It has been speculated that this may be a common mechanism of tumorigenesis regardless of etiology. However, studies on the expression of onc genes in human tumors are so far inconclusive. Added to the list of retroviruses that are associated with leukemias is a human retrovirus called HTLV, repeatedly isolated from T-cell lymphoma and leukemia cells that had been established in culture with T-cell growth factor. HTLV is an exogenous type-C virus distinguished from other mammalian retroviruses by assays of nucleid acid homology and immunologic assays of viral proteins. The amino acid sequence of the purified core antigen (p24) revealed a distant but significant homology to bovine leukemia virus p24. Transmission of the virus has been successful with T lymphocytes from relatives of HTLV-positive T-cell leukemia patients (i.e., antigen or antibody-positive patients) and more recently to normal human cord blood T lymphocytes. These data suggest a T-cell tropism for HTLV and a possible genetic factor for susceptibility to HTLV infection. A wide survey of human sera for antibodies to HTLV was conducted. Among those positive for antibodies to p24 and p19 were almost all serum samples from Japanese patients with adult T-cell leukemia, a disease that is endemic in South-Western Japan. A similar phenomenon has also been found in other parts of the world, especially in the West Indian black population. These results indicate that HTLV is much more prevalent in certain geographical regions than in others. The biochemical characterization of HTLV and sero-epidemiologic studies demonstrate that HTLV is a unique retrovirus and suggest that it may be etiologically involved with certain forms of adult T-cell leukemia and lymphoma. Many more epidemiologic surveys for HTLV and studies of its molecular mechanism of influencing T-cell proliferation are needed.