Evidence for human T cell lymphoma-leukemia virus infection of family members of human T cell lymphoma-leukemia virus positive T cell leukemia-lymphoma patients

Sera of family members of patients from the United States, the Caribbean, and Japan, with human T cell lymphoma-leukemia virus (HTLV) associated T cell malignancies, possess HTLV-specific antibodies directed against internal structural components of HTLV, p24 and p19. The prevalence of antibodies to HTLV is greater in family members than in random healthy donors, which supports the infectious nature of HTLV and its association with particular aggressive T cell malignancies. Expression of HTLV p24 and p19 has also been observed in cultured T cells of some healthy relatives, and intact virus particles have been released from cells of one possibly pre-leukemic family member.     

Markers of health status in an HTLV-I-positive cohort.

The health effects of chronic human T-cell lymphotropic virus type I (HTLV-I) infection were examined in a cohort of Japanese men who had emigrated from Okinawa, Japan, and had been participants in a prospective study in Hawaii since 1965. In the present follow-up study carried out in 1987-1988, various health indicators were measured in the subjects, whose mean age was 72.5 years. Participation rates were lower in the HTLV-I seropositives than in the seronegatives (46.7% vs. 76.0%) in the > or = 75-year age group. Lack of participation was significantly correlated with a high HTLV-I antibody titer. Among the participants, seropositive subjects were significantly more likely than the seronegatives to have lymphocytopenia (32.7% vs. 17.7%) and mild anemia (25.5% vs. 14.1%) after adjustment for age and socioeconomic status. The seropositives also had a higher frequency of acupuncture therapy (age-adjusted odds ratios were 2.1 and 4.2 for 1-5 treatments and > or = 6 treatments, respectively). Proportions of subjects who had been hospitalized at least twice were higher among the seropositives in the oldest age groups, 70-74 years and > or = 75 years, but not in those aged 65-69 years. Although specific disease conditions were not identified in this study, hematologic data, treatment histories, and the correlation between participation status and HTLV-I antibody titers suggest that chronic HTLV-I infection may be associated with as yet undefined adverse health effects, particularly in older age groups.     

Higher macrophage inflammatory protein (MIP)-1alpha and MIP-1beta levels from CD8+ T cells are associated with asymptomatic HIV-1 infection

To test the hypothesis that beta-chemokine levels may be relevant to the control of HIV in vivo, we compared RANTES, MIP-1alpha, and MIP-1beta production from purified CD8(+) T cells from 81 HIV-infected subjects and from 28 uninfected donors. Asymptomatic HIV(+) subjects produced significantly higher levels of MIP-1alpha and MIP-1beta, but not RANTES, than uninfected donors or patients that progressed to AIDS. In contrast, beta chemokines in plasma were either nondetectable or showed no correlation with clinical status. The high beta-chemokine-mediated anti-HIV activity was against the macrophage tropic isolate HIV-1(BAL), with no demonstrable effect on the replication of the T-cell tropic HIV-1(IIIB). These findings suggest that constitutive beta-chemokine production may play an important role in the outcome of HIV-1 infection.     

Segregation of human T cell lymphotropic virus type I and II infections by antibody reactivity to unique viral epitopes.

A recombinant protein of the human T cell lymphotropic virus type I (HTLV-I) gp46 outer membrane envelope, MTA-4 (residues 129-203), reacted by Western blot with sera from HTLV-I-infected individuals from the United States and Jamaica but not with 24 (10%) of 242 Japanese sera. A related gp46 recombinant protein, MTA-1 (residues 162-209), reacted with all 58 sera from HTLV-I-infected US and Jamaican individuals and 238 of 242 sera from infected Japanese (combined sensitivity of 99%). Neither recombinant showed reactivity to sera from HTLV-II-infected individuals or uninfected controls. The reactivity of recombinant proteins containing the region of HTLV-II gp46 analogous to MTA-1 was also evaluated by Western blot: GH2-K15 (residues 157-205) and GH2-K55 (residues 162-205) reacted with 88 (98%) and 89 (99%), respectively, of 90 sera from HTLV-II-infected individuals but not with sera from HTLV-I-infected individuals or uninfected controls. These recombinant proteins should permit the development of assays to unambiguously confirm and differentiate HTLV-I and HTLV-II infections.     

Endemic human T cell lymphotropic virus type II infection among isolated Brazilian Amerindians.

Evidence for human T cell lymphotropic viruses (HTLV) was sought in sera and cells collected from adults in 13 isolated South and Central American Indian tribes. Serologic tests identified frequent HTLV-II-like reactivity among the Cayapo and Kraho tribes, who live 330 km apart in Central Brazil. Polymerase chain reaction analyses of viral DNA in cell pellet and plasma fractions confirmed the virus as HTLV-II. Both tribes speak Gé and, at the time of blood collection (1974), subsisted as hunter/gatherers and slash and burn agriculturalists. Further testing of plasma from Cayapo and Kraho of all ages revealed overall HTLV-II prevalence rates of 33.3% and 12.2%, respectively, with increasing prevalence associated with age and female gender. These data reveal for the first time a high prevalence of HTLV-II infection in remote South American Indians with little contact with non-Indians. Thus, HTLV-II is postulated to be an ancient human virus in the New World.     

The human T-cell leukemia/lymphoma virus, lymphoma, lytic bone lesions, and hypercalcemia

The human T-cell lymphoma (HTL) virus is a type C RNA tumor virus isolated from patients with malignancies of mature T cells. We report three patients with peripheral T-cell lymphoma, hypercalcemia, and antibodies to HTL virus. One patient presented with idiopathic hypercalcemia of 6 months' duration, two with striking lytic bone lesions, and two with circulating malignant lymphocytes. Malignant cells from all patients had surface markers characteristic of thymic-derived lymphocytes (T cells), and all patients had natural serum antibodies to disrupted HTL virus and to one or both viral structural proteins p19 and p24. Patients with adult peripheral T-cell lymphomas, particularly those that present with hypercalcemia and lytic bone lesions, may have antibodies to the type C RNA human tumor virus, HTL virus.