Spectrum of natural antibodies against five HTLV-III antigens in infected individuals: correlation of antibody prevalence with clinical status.

The genome of the HTLV-III/LAV retrovirus, the etiologic agent of the acquired immunodeficiency syndrome (AIDS), encodes the viral structural proteins (envelope and core proteins), the reverse transcriptase, a transactivation protein (tat-III), as well as two other proteins (3'orf, sor) of unknown function. We studied the prevalence of natural antibodies against envelope, gag, 3'orf, sor, and tat-III in the sera of HTLV-III infected individuals in an attempt to correlate clinical status with seropositivity to specific HTLV-III antigens. We selected 101 sera; 16 were obtained from normal donors with no known risk factors, and 85 were from patients with full-fledged AIDS (28 cases), AIDS-related complex (ARC, 22 cases), and healthy people at risk (homosexuals, intravenous [IV] drug users, relatives of AIDS patients; 35 cases). Seropositivity for antibodies against the envelope (gp41) and gag antigens (p15, p24) was determined by Western blot using disrupted HTLV-III virions. Of the 101 sera, all 16 from nonrisk donors and 3/35 from healthy at-risk donors were negative for antibodies against either the gp41 or p15 and p24. The remaining 82 sera were seropositive for either the gp41 and/or the p15 and p24. All sera were then tested against the three known HTLV-III antigens (3'orf, sor, and tat-III) that have been synthesized in bacteria. Our data indicate that all the HTLV-III antigens tested are immunogenic in vivo. No significant difference in antibody prevalence to gp41 (close to 100%) and to the 3'orf, sor, and tat-III proteins (approximately 50%) was observed with regard to stage of the disease. In contrast, the prevalence of antibodies against the core antigens decreased from approximately 100% in infected people with no clinical signs of disease to 50% in ARC and AIDS patients. The percentage of patients seropositive for all five antigens tested was increased in the AIDS group. These results indicate that the greatest antibody prevalence was obtained using viral envelope antigen and further suggest that screening with the newly identified 3'orf, sor, and tat-III proteins as antigens would confer no further diagnostic advantage. The pattern of natural antibodies observed during disease progression did not suggest any pathogenetic mechanism.