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Of 96 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and healthy individuals at risk for AIDS, 4 had no detectable antibodies to viral proteins, though human T-cell leukaemia (lymphotropic) virus type III was isolated from their lymphocytes. 3 of these subjects were symptom-free and 1 had lymphadenopathy. All 4 were sexual partners of patients with AIDS or AIDS-related complex. The occurrence of seronegative but virus-positive persons without clinical symptoms suggests that assays other than those detecting antibody to virus, perhaps based on detection of viral antigens or immune complexes, may be required to identify all infected individuals.

An assay for antibodies to membrane antigens of cells infected by human T-cell leukemia virus was used to examine serum from persons who donated blood to 12 patients with acquired immunodeficiency syndrome (AIDS) associated with blood transfusions. The occurrence of positive results in the assay was significantly greater among donors to the AIDS patients (9 of 117; 7.7 percent) than among random donors (1 of 298; 0.3 percent). Of 12 sets of donors examined, 9 sets included a donor whose serum gave positive results for the presence of the antibodies. In six of these nine sets, the seropositive donor was an individual who was also identified as a possible source of AIDS transmission when epidemiologic and immunologic criteria were used.

We tested serum samples from 50 hemophiliacs from Sevilla, Spain, for antibody to HTLV-III by indirect membrane immunofluorescence (IMI) and radioimmunoprecipitation with SDS polyacrylamide gel electrophoresis (RIP-SDS/PAGE). All had received commercial clotting factors from the United States with the exception of one hemophiliac who had never been transfused. Thirty-four (68%) reacted with HTLV-III-infected cells (H9/HTLV-III) by both methods, but not with the uninfected line (H9). Of 41 hemophilia-A patients tested, 28 (68%) were positive, and of nine hemophilia-B patients, six (66%) were positive. The nontransfused hemophilia-B patient was negative for antibody to HTLV-III by both methods. One patient with clinical AIDS tested positive as did six of seven with chronic unexplained lymphadenopathy. The eight individuals with AIDS or lymphadenopathy all had hemophilia A. We conclude that exposure to HTLV-III is widespread among asymptomatic hemophiliacs in Spain.

Along with homosexual men, Haitians, and intravenous drug abusers, hemophiliacs are at high risk of contracting acquired immunodeficiency syndrome (AIDS). An earlier study revealed that 36 percent of a group of the AIDS patients had antibodies to cell membrane antigens associated with the human T-cell leukemia virus (HTLV-MA), whereas only 1.2 percent of matched asymptomatic homosexual controls had these antibodies. In the present experiments, serum samples from 172 asymptomatic hemophiliacs were examined for the presence of antibodies to HTLV-MA. Such antibodies were detected in 5 to 19 percent of the hemophiliacs examined from four geographical locations, but in only 1 percent or less of laboratory workers, normal blood donors, donors on hemodialysis, or donors with chronic active hepatitis.

Of 45 individuals seropositive for human T cell lymphotropic virus type III/lymphadenopathy-associated virus, 45 were found to have detectable salivary antibodies to viral antigens by a radioimmunoprecipitation assay. The results also showed that a Western blot assay for salivary antibodies may be possible. The feasibility of a diagnostic test for human T cell lymphotropic virus type III/lymphadenopathy-associated virus not requiring venipuncture is discussed.

Sera from hemophiliacs were analyzed for antibodies to human immunodeficiency virus type 1 (HIV-1) by using radioimmunoprecipitation (RIP), western blotting (WB) with nonreducing buffer (NR), and WB with reducing buffer (R). We analyzed envelope gp160, gp120, and gp41; pol gene proteins p64, p53, and p34; and gag gene protein p24. Of 215 samples positive for reactivity to gp160 and gp120(RIP), antibodies to p24 were undetectable in 2 (0.9%), to gp41 in 9 (4.2%), to the pol antigens in 5 (2.3%), to gp120(NR) in 3 (1.4%), and to gp120(R) in 55 (25.6%). By sequential analysis of samples, antibodies to gp120(NR), gp120(R), p24, gp41, p64/53, and p34 were observed later in the course of infection than were antibodies to gp120(RIP) or gp160. This result suggests caution against reliance on WB as the "gold standard." A significantly higher rate of progression to AIDS-related complex was found for individuals lacking antibodies to gp120(R). It is possible that antigenic domains represented by gp120(R) may play a role in the pathogenesis of HIV-1 infection.

Recently, antibodies to human T-cell leukemia virus membrane antigens (HTLV-MA) and elevated levels of beta 2-microglobulin and thymosin alpha 1 have been found with high frequency in patients with the acquired immunodeficiency syndrome. Prospective studies of asymptomatic persons at high risk for this syndrome will ascertain whether any of these findings is a predictive marker for the disease. In this study, antibodies to HTLV-MA, beta 2-microglobulin levels, and thymosin alpha 1 levels were determined for a group of asymptomatic adult hemophiliacs and their wives. Five of thirty-nine hemophiliacs had HTLV-MA antibody, compared with none of 21 wives tested. The mean beta 2-microglobulin level for hemophiliacs was significantly higher than the control value (p less than 0.001), whereas the wives had a normal mean value. The mean thymosin alpha 1 values were normal for hemophiliacs and their wives; however, 3 of 22 hemophiliacs and 1 of 16 wives had abnormally high levels. Whether any of these abnormalities correlate with subsequent development of the acquired immunodeficiency syndrome will be ascertained by longitudinal follow-up of this population.

In this study, two glycoproteins (gp160 and gp120) that are encoded by human T-cell lymphoma virus type III (HTLV-III) were the antigens most consistently recognized by antibodies found in patients with the acquired immune deficiency syndrome (AIDS) and with the AIDS-related complex (ARC) and in healthy homosexual males. The techniques used to detect the glycoproteins were radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (RIP/SDS-PAGE). Although most antibody-positive samples from ARC patients and from healthy homosexual males also reacted with the virus core protein p24, less than half of the AIDS patients revealed a positive band with p24 under the same conditions. The ability to detect antibodies against a profile of both the major env gene encoded antigens and the gag gene encoded antigens suggests that the RIP/SDS-PAGE may be a valuable confirmatory assay for establishing the presence or absence of antibodies to HTLV-III in human serum samples.

We studied 66 Israeli hemophiliacs for antibodies to HIV in blood samples collected between 1978 and 1985. By May 1985, 2 had AIDS, 2 had ARC, 4 had lymphadenopathy with some immunologic dysfunction, and 58 were asymptomatic. Antibodies to HIV were detected in 40 (60.6%) patients, including all 8 with disease. Presence of HIV antibodies was significantly associated with receipt of non-heat-treated commercial factor VIII concentrates (NHT fac VIII) between 1980 and 1983. Thirty-eight of 45 (84.44%) patients treated with NHT fac VIII developed antibodies to HIV, compared to 1 of 16 (6.25%) treated with cryoprecipitates and fresh plasma only. Of 40 seropositive patients, 1 (2.5%) had antibodies by 1980, 4 (10%) by 1982, 14 (35%) by 1983, 10 (25.0%) by 1984, and 11 (27.5%) by May 1985. The decline in the rate of seroconversion can be attributed to the replacement of NHT fac VIII concentrate with heat-inactivated factor VIII (HT fac VIII) concentrate by November 1983. As of January 1984 only HT fac VIII was administered. Twenty-nine multitransfused thalassemia patients as well as 20 healthy Israeli blood donors were seronegative to HIV. All 40 (100%) seropositive hemophiliacs had antibodies to viral env gene encoded gp120/gp160 antigens. Twenty-four (60.05%) also had antibodies to viral gag gene encoded p24 and/or p55 antigens. While antibodies to gp120/160 persisted during the follow-up time, a loss of antibodies to p24/55 was observed in 5 of 16 (31.25%) seropositive patients from whom multiple samples were available. gp120/160 positive, p24/55 negative hemophiliacs had significantly lower absolute T-helper cell counts and reversed Th/Ts ratios when compared to gp120/160 p24/55 seropositive patients. Four of the 16 (25.0%) asymptomatic gp120/160 positive, p24/55 negative patients developed overt disease within 15 months of the last blood collection. The data suggest that exposure to HIV antigens is widespread among hemophiliacs in Israel, and can be attributed to receipt of NHT fac VIII concentrates prior to 1984. Antibodies to gp120/160 are of the most important diagnostic value while loss of antibodies to p24/p55 may be of prognostic value.

The present studies were initiated to define the coding region of a 34 kilodalton (kd) protein (p34) frequently observed with antibodies from HTLV-III/LAV-infected people by immunoblotting and radioimmunoprecipitation (RIP) techniques. We have directly mapped this viral protein to the pol gene of HTLV-III/LAV by radiolabeled amino acid sequence analysis. This region at the 3' end of the pol gene is predicted to encode the endonuclease/integrase of the virus. The seroprevalence rate of antibodies to the pol gene products p64 and p53 and to the endonuclease p34 were evaluated. Of 161 HTLV-III/LAV seropositive people tested by immunoblotting procedures, greater than 98% had antibodies which reacted to p64/p53 and 92.6% reacted to p34 indicating that these viral proteins are highly immunogenic in nature. We have also analyzed the serum of nine healthy people living in West Africa who were infected with HTLV-IV, a closely related retrovirus. Nine of nine seropositive people had antibodies that cross-reacted to p34 of HTLV-III/LAV, whereas only seven of nine reacted to p64/p53. These studies and our earlier observations indicate that current diagnostic procedures for screening for HTLV-III/LAV infection may also detect HTLV-IV seropositive individuals, pointing to a need for more specific assay systems.

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)

Human T-cell leukaemia virus type III (HTLV-III) is suspected of having a key role in the pathogenesis of acquired immune deficiency syndrome (AIDS). Epidemiological data suggest that AIDS is transmitted by an infectious agent through intimate contact with body secretions, blood or blood products. To maintain haemostasis, many haemophiliac patients depend on commercially prepared clotting concentrates made from large multi-donor plasma pools and are thus at increased risk of developing the disease. We report here that, using indirect membrane immunofluorescence and radioimmunoprecipitation with SDS-polyacrylamide gel electrophoresis, we have detected antibodies to HTLV-III in 30 of 47 (64%) asymptomatic haemophiliacs and in all of three haemophiliacs who either had or soon developed AIDS. Of 34 samples drawn before 1984, 18 (53%) were antibody-positive, whereas of 16 samples drawn during 1984, 15 (94%) were positive (P less than or equal to 0.002). These data suggest that exposure to HTLV-III antigens is widespread among asymptomatic haemophiliacs.

The human T-lymphotropic virus type III (HTLV-III) is the primary cause of the acquired immunodeficiency syndrome (AIDS) and related disorders (ARC). Prior studies have reported that nearly all symptomatic patients with AIDS or ARC manifest antibody to HTLV-III. This observation has engendered efforts to screen for HTLV-III, especially prior to blood donation, with assays for antibody to HTLV-III. We report the first two cases, one with AIDS and one with ARC, that are HTLV-III virus positive but antibody negative. Accurate diagnosis of HTLV-III infection in some cases may require direct virus culture or tests for antigen. In addition, lack of HTLV-III antibody may indicate an atypical clinical course of AIDS.

Human T cell leukaemia virus (HTLV), HTLV proviral DNA, and antibodies to HTLV or a related agent have recently been detected in patients with acquired immunodeficiency syndrome (AIDS). Antibodies against HTLV-related antigens were assayed by means of indirect living cell immunofluorescence of HTLV-infected cells in sera recently collected from Georgia haemophiliacs and in sera collected between 1976 and 1981 from New York haemophiliacs. 5 of 45 Georgia haemophiliacs and 8 of 48 New York haemophiliacs had antibodies to HTLV-associated cell membrane antigen (HTLV-MA). None of the control Georgia patients on haemodialysis or with chronic hepatitis had detectable antibodies. The 5 haemophiliac patients from Georgia with HTLV-MA had significantly fewer T4 lymphocytes than similar HTLV-MA-negative patients. There were no other significant immunological differences between these groups. These data suggest that transfusions with blood products may expose haemophiliacs to a substantial risk of acquiring HTLV or a related virus.

The acquired immune deficiency syndrome (AIDS), which has recently occurred at increasing rates in homosexual men, intravenous drug users, and others, is characterized by the development of Kaposi's sarcoma and several opportunistic infections including pneumonia caused by Pneumocystis carinii. Serum samples from patients with AIDS and from matched and unmatched control subjects were examined for the presence of antibodies to cell membrane antigens associated with human T-cell leukemia virus. Nineteen of 75 of the AIDS patients had antibodies directed to surface antigens of Hut 102, a reference T lymphoid cell line infected with leukemia virus, as did two of the 336 control subjects.

A proportion of the plasma for the triply inactivated, plasma-derived hepatitis B vaccine produced in the United States is obtained from homosexual men. Because homosexual men are a high-risk group for the acquired immunodeficiency syndrome (AIDS), concern has emerged that the vaccine could harbor the AIDS agent. To evaluate this risk, we tested 15-month postvaccination serum samples for antibodies to human T-cell lymphotropic virus type III in 100 health care workers who had received inactivated hepatitis B vaccine lots made from plasma collected between 1977 and 1979 and 100 who had received placebo injections. None of the 200 health workers had serological evidence of human T-cell lymphotropic virus type III infection. These serological findings lend additional support to earlier epidemiologic and immunologic observations suggesting that hepatitis B vaccine does not transmit infection with an AIDS virus.

A newly identified protein from HTLV-III/LAV, the virus implicated as the etiologic agent of the acquired immune deficiency syndrome, was studied. This protein, which has a molecular weight of 27,000 (p27), was shown by amino acid sequencing to have a coding origin 3' to the env gene on the HTLV-III genome. The presence of antibodies to p27 in virus-exposed individuals indicated that this gene is functional in the natural host.

Whole saliva samples collected from available people at risk in Boston for infection with human T-lymphotropic virus type III (HTLV-III/LAV), from late 1984 through early 1985, were analyzed for the presence of antibodies to viral proteins. Fourteen of 20 (70%) acquired immunodeficiency syndrome (AIDS) patients and 14 of 15 (93%) AIDS-related complex (ARC) patients had salivary antibodies that reacted with the virus-encoded glycoproteins gp160 and gp120 of HTLV-III infected cells. All of the AIDS and ARC patients had serum antibodies to the same antigens. Of 20 sex partners of AIDS/ARC patients, nine (45%) showed anti-HTLV-III antibodies, and four of 18 (22%) healthy homosexual males also were positive for such antibodies. Serum and salivary antibody status were the same in these groups. A minority of those patients positive for salivary antibodies to env gene-encoded gp160 and gp120 also had salivary antibodies to gag gene-encoded proteins of 55,000, 24,000, and/or 17,000 daltons. Immunoglobulin A (IgA) class antibodies comprised the majority of the salivary antibody response. The spectrum of HTLV-III proteins detected by the salivary and serum antibodies was similar. The possibility that secretory IgA from the gut-associated lymphoid system may play a role to restrict salivary transmission of HTLV-III should be considered.