HUMAN T-CELL LEUKEMIA VIRUS TYPES I AND II

Isolation of the first pathogenic human retrovirus was reported in 1980 (Poiesz et al., 1980) and was soon followed by the isolation of a second, closely related but distinct virus (Kalyanaraman et al., 1982). These viruses subsequently became known as human T-cell leukemia virus types I and II (HTLV-I, HTLV-II); they are sometimes referred to as human T-lymphotropic viruses. Multiple isolates of the HTLVs have now been obtained, novel regulatory properties identified, and areas of endemicity throughout the world defined by seroepidemiological studies.

Although HTLV-II has not been linked definitively to a specific disease, HTLV-I has been shown to be etiologically associated with two very different diseases. The first, adult T-cell leukemia/lymphoma (ATLL), for which the virus is named, was first described in southern Japan (Uchiyama et al., 1977), where the virus is endemic. ATLL is a malignancy primarily of CD4+ (T-helper/inducer) lymphocytes, and in the leukemic phase, the HTLV-I provirus is monoclonally integrated into the DNA of neoplastic cells. The onset of disease occurs many years after the initial infection, and the most severe forms of the disease are characterized by generalized lymphadenopathy, visceral and cutaneous involvement, and bone lesions (Kuefler and Bunn, 1986). Effective treatment is not available, and death usually occurs within one year of diagnosis. Fortunately, only 2 to 5 percent of HTLV-I-infected persons develop ATLL (Murphy et al., 1989).

The second HTLV-I-associated disease is a neurological condition called tropical spastic paraparesis (TSP), which was first described in the Caribbean (Gessain et al., 1985). The same syndrome was subsequently described by doctors in Japan, who called it HTLV-I-associated myelopathy (HAM) (Osame et al., 1986). This disease, which is now usually referred to as TSP/HAM, begins with difficulties in walking and weakness and spasticity in the legs; it can also include back pain, sensory disturbances, urinary incontinence, and impotence in men. Disability progresses over several years, and eventually victims may become confined to a wheelchair. Because afflicted individuals have high concentrations of HTLV-I-specific antibodies in serum and spinal fluid (Osame et al., 1990), sometimes in association with an human leukocyte antigen (HLA)-linked high immune responsiveness to HTLV-I (Usuku et al., 1988), some investigators feel that TSP/HAM is an immunological disease triggered by the virus. As with ATLL, TSP/HAM occurs in a small percentage (about 1 percent) of HTLV-I-infected persons (Kaplan et al., 1990).

Interest in HTLV-I increased with the in vitro observation of several investigators that the efficiency of replication of HIV, the virus that causes



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