SEQUENCE-ANALYSIS OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) ENV GENES AMPLIFIED FROM CENTRAL-NERVOUS-SYSTEM TISSUES OF PATIENTS WITH HTLV-I-ASSOCIATED MYELOPATHY OR LEUKEMIA

Human T cell lymphotropic virus type I (HTLV-I) is a retrovirus that h as been linked to HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), a chronic or inflammatory neurological disease with some resemblance to multiple sclerosis. We used the polymerase chain reaction to amplify viral env genes in foci of inflammation and demyel ination in the nervous system to adduce additional evidence of the ass ociation of HTLV-I with the neuropathological changes in HAM/TSP, and document in this report such an association. We also sought evidence o f a distinct viral species in the lesions by amplifying, cloning and s equencing the env genes from tissues sections in which there were path ological changes. We did not find changes in the env gene that correla ted with HTLV-I-associated neurological disease vs adult T cell leukem ia or with the nervous system vs peripheral blood and lymphoid organs. We did, however, find evidence of extensive mutation and possibly del etions in the env gene in HTLV-I-associated neurological disease. We i nterpret these findings of increased genetic diversity as a reflection of higher rates of viral replication in HTLV-I-associated myelopathy that support a model of pathogenesis in which increased viral replicat ion activates immune cells that subsequently enter the nervous system and cause injury by immunopathological mechanisms. (C) 1995 Academic P ress Limited