Detection methods for the human T-cell leukemia virus type-I (HTLV-I) for blood screening and diagnosis generally rely on antibody tests that use the structural proteins of HTLV-I as antigen. We have found an unusual pattern of antibody reactivity among people who are at high risk of HTLV infection due to being a family member of an adult T-cell leukemia (ATL) patient: a specific antibody reaction exclusively directed to the HTLV regulatory protein tax, and not to the HTLV-I structural proteins. Sera from 7 of 82 (8.5%) structural antibody- undetectable family members of ATL patients had the anti-tax reactivity. Two seroconverters were observed. One seroconverter a healthy resident of Miyazaki, tested negative for structural antibody, but positive for tax antibody. Two years later she tested positive for both. The other seroconverter, an Israeli hemophiliac, tested negative for both antibodies, but converted to tax antibody-positive/structural antibody-negative. The HTLV-I tax-only antibody profile was also observed in sera sets from two other populations at risk for HTLV infection, human immunodeficiency virus-1-infected patients at the Bronx-Lebanon Hospital in New York and Israeli hemophiliacs. DNA samples from lymphocytes of four individuals with antibody reactivity only to HTLV-I tax were tested in polymerase chain reaction experiments; no HTLV-I or -II DNA was detected.

We studied 1508 individuals from Zaire, Burundi, Tanzania, Zambia, Kenya, and Cameroon for antibodies to HIV-2/HTLV-4. AIDS, ARC, other disease or tumor patients and healthy people were sampled from 1984-1986. By radioimmunoprecipitation and SDS/PAGE analysis and/or Western blot we failed to find any samples with specific antibodies to HIV-2/HTLV-4 indicative of infection. In contrast, 363 of these 1508 individuals demonstrated antibodies to HIV-1/HTLV-3B by the same serologic assays. HIV-2/HTLV-4 infection appears to be quite rare in Central Africa. AIDS and related syndromes in this study were exclusively correlated with HIV-1 infection. Studies in West Africa have shown high rates of infection with HIV-2/HTLV-4 where cases of AIDS are still relatively uncommon. These results indicate that HIV-2/HTLV-4 has a distinct geographic distribution from that of HIV-1 in Africa. Further studies are necessary to better define the pathogenicity and natural history of this distinct new virus, HIV-2/HTLV-4.

T-lymphotropic retroviruses of cats cause lymphopenia and immunosuppression and represent the major cause of death in that species. Similarly HTLV-I which is T4 tropic is associated with an increased risk for development of infectious disease in regions where the virus is endemic. Since HTLV-I is also believed to be transmitted by blood and by sexual intercourse we considered the possibility that a variant form of HTLV might cause AIDS. The identification of cross-reactive antibodies to HTLV-I-MA in a third or more of the AIDS patients and in suspicious blood donors that donated to transfusion-associated cases of AIDS eventually led to the recognition of HTLV-III, the causative agent of AIDS. The protein most associated with lymphocyte immortalization or transformation in the case of HTLV-I is p42. The proteins of HTLV-I encoded by the amino terminus of the env gene designated gp61 and gp45 are the most immunogenic antigens of this virus. Similarly those encoded by the amino terminus of the env gene HTLV-III designated gp160 and gp120 appear to be the most immunogenic markers for this agent. Almost all AIDS patients, ARC patients, and asymptomatic hemophiliacs have detectable antibodies to gp120 and gp160. HTLV-III related agents designated STLV-III have been found in macaque monkeys that develop simian AIDS and high prevalence rates of antibodies to STLV-III can be found in healthy African green monkeys. We hypothesize that the STLV-III of African green monkeys could represent a recent source of the virus to have infected humans in central Africa where the human epidemic probably began. The recognition that up to one million people may already be infected with HTLV-III in the United States alone indicates the need for development of a vaccine. The availability of primate species infected with the serologically related STLV-III agents that either resist disease development (African green monkeys) or succumb to an AIDS-type syndrome (rhesus) provide models that should aid in our attempts to develop such vaccines.

Antigens encoded by the gag and env genes of the human T-lymphotropic virus type III/lymphadenopathy associated virus (HTLV-III/LAV) include a p55 gag polyprotein that yields p24 as the major virus core protein, and an env gene polyprotein, gp 160, that produces gp 120, the most immunogenic protein in humans, at the amino terminus. Although its use is limited to research laboratories due to the cost and specialized procedures involved, the analysis of sera by radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis is the test providing the optimal balance of specificity and sensitivity. Because the gp 120 represents the external virus protein, it would be the most appropriate antigen for vaccine development. Also viruses serologically related to HTLV-III/LAV were detected recently in two species of Old World monkeys. Because about half the healthy African green monkeys appear to have been exposed to simian T-lymphotropic virus type III (STLV-III), a related agent of the species, a characterization of the STLV-III gp 120 and immune response of the host may provide additional information for vaccine development.

There is increasing evidence for the link between members of the human T-lymphotropic virus family and clinically important disease. We used indirect membrane immunofluorescence (IMI) to screen patient and control sera for antibodies to human T-cell leukemia virus (HTLV) specific cell membrane antigens (HTLV-MA) of HTLV-I and HTLV-III. Representative sera were screened for antibodies to specific HTLV-encoded proteins using radioimmunoprecipitation (RIP) with SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Essentially all Japanese patients with adult T-cell leukemia/lymphoma (ATLL) from Miyazaki, Japan had detectable antibodies to HTLV-I-MA, further supporting the evidence for the probable etiologic relationship of HTLV-I and ATLL. While 16% of the healthy adults from this endemic region had antibodies to HTLV-I-MA, such antibodies were also found in 42% of the adults hospitalized in Miyazaki with severe infections diseases. Other studies have demonstrated HTLV-I antibodies in 12% of asymptomatic hemophiliacs examined from various U.S. cities. We have previously shown that HTLV-I status positive antibody in hemophiliacs is accompanied by a decrease in the number of T helper cells. Patients seropositive for antibodies to HTLV-I-MA regularly demonstrated antibodies to the env gene encoded gp61 proteins, while lower but significant proportions had antibodies to the gag and lor gene proteins. These and other observations suggest that infection with at least some strains of HTLV-I may be associated with mild or transient immunosuppression, in the absence of leukemia. Analysis by RIP indicated that gp61 and gp45, both encoded by the env gene of HTLV-I, are the most immunogenic proteins of the virus. The gp61 HTLV-I is highly crossreactive with gp67, the major env protein of HTLV-II. Patients with acquired immune deficiency syndrome (AIDS) were also examined for antibodies to HTLV-I-MA and antibodies to the gag, env, and lor gene proteins by RIP. Antibodies were detected in 38-75% of the patients, the higher percentage reflecting the presence of at least one positive sample in those individuals where more than three serial serum samples were tested. Numerous control groups were essentially seronegative for antibodies to HTLV-I proteins. When AIDS patient sera were examined for antibodies to HTLV-III, 95-100% were seropositive. Such antibodies were also found in the majority of asymptomatic Boston-areas hemophiliacs.(ABSTRACT TRUNCATED AT 400 WORDS)