Antibodies Reactive with Human T-Lymphotropic Retroviruses (HTLV-111) in the Serum of Patients with AIDS

In cuts, infection with T-lymphotropic retroviruses can cause T-cell proliferation and leukemia or 7'-cell depletion and immunosuppression. In humans, some highly T4 tropic retroviruses called HTLV-I cun cuuse T-cell proliferation and leukrmiu. The subgroup HTLV-I1 ulso induces T-cell prol(ferution in vitro, but its role in disease is uncleur. Viruses of u third subgroup of humun T-lymphotropic retroviruses, collectively designated IfTLV-111, have been isolated Jiom cultured cells o f48 patients with acquired immunodeficiency syndrome (AIDS). The biologicul properties of HTLV-Ill und immunologicul analyses of its proteins show thut this virus is a member oj'the HTLV family, und that it is more closely reluted to HTLV-I1 than to NTLV-I. Serum samplesfiom 88 percent ofputients with AIDS undf iom 79 percent oj'hornosexuul men with signs und syrnptoms thut frequently prrcede AILIS, but Jiom less thun I percent of heterosexual subjects, have antibodies reuctive against untigens of 1f7'LV-Ill. The major immune reactivity uppeurs to be directed ugainst p41, the presumed envelope antigen of the virus. The incidence of the acquired helper functions, including production of immunodeficiency syndrome (AIDS) in antibodies by B cells (1, 3). homosexual men with multiple sexual Retrovirus infections are known to partners, intravenous drug abusers, helead to depressed immune functions in mophiliacs, blood transfusion recipients, animal systems. For example, in cats, a and close heterosexual contacts of memmajor result of infection with feline leubers of these high-risk groups (1-7) kemia virus (FeLV) is loss of normal strongly suggests that the disease immune f~~nction. More Fe1,V-infected spreads by the transmission of an infeccats die from consequences of this imtious agent (8, 9). The agent's primary mune dysfunction than from the leuketargets within the body appear to be mia itself (10). Fe1.V provides an examspecific subpopulations of T cells. The ple of a single T-cell tropic retrovirus severe immune deficiency of AIDS pathat causes both target cell proliferation tients results from an unusually low pro(leukemia) and depletion (irnmunosupportion of helper T lymphocytes pression). By analogy, a human retrovi(OKT4') and a resulting lack of many rus with a tropism for T cells should be Table 1. Antibodies to HrI>V-III in serum samples from patients with AlDS and pre-AIDS and from control subjects. Wells of 96-well Immulon plates were coated overnight with a lysate of density-banded IITLV-Ill (30) at 0.5 p.g protein per well in 100 ~1 50 mM sodium bicarbonate buffer, p H 9.0. ?'he wells were washed with water and incubated for 20 minutes with 100 p.1 of 5 percent bovine serum albumin in phosphate buffered saline (PBS). The wells were washed again in water, and then 100 p.1 of 20 percent normal goat serum in PHS were added to each well, followed by 5 or 10 p.1 of the test sera. These were allowed to react for 2 hours at room temperature. ?'he wells were washed three times with 0.05 percent Tween-20 in PBS and incubated for 1 hour at room temperature with peroxidase-labeled goat antiserum to human immunoglobulin ti at a dilution of 1 : 2000 in I percent normal goat serum in PHS. The wells were successively washed four times with 0.05 percent Tween-20 in PBS and four times with PBS and reacted with 100 p. 1 of the substrate mixture containing 0.05 percent orthophenylene diamine and 0.005 percent hydrogen peroxide in phosphate-citrate buffer, pH 5.0. The reactions were stopped by the addition of 50 p. 1 of 4N H,SO,, and the color yield was measured with a Dynatech ELlSA reader. Assays were done in duplicate and absorbance reading greater than three times the average of four normal negative control readings was taken as positive. ~ ---~ ~ Number positive Number Percent for antibodies to I-II'LV-I I I tested positive