Human T-lymphotropic Virus Type III Infection Research Articles

Anticardiolipin antibodies associated with HTLV-III infection.

Anticardiolipin antibody levels were determined in 73 homosexual men. Thirty of these patients had acquired immunodeficiency syndrome (AIDS), 16 patients had the AIDS-related complex (ARC) and 27 were healthy. Antibodies to human T-lymphotropic virus type III (HTLV-III) were detected in all patients with AIDS and ARC and in 11 of the healthy homosexuals. Eight patients with positive fluorescent treponemal antibody absorption test were excluded from the study. High levels of IgG-anticardiolipin antibodies were present in 23 of the 28 patients with AIDS; 12 of the 14 with ARC; five of the 10 HTLV-III positive healthy homosexuals; and none of the 13 HTLV-III negative healthy homosexuals. High levels of IgM-ACA were detected only in four patients with AIDS. The IgG-anticardiolipin levels were higher in the HTLV-III positive patients than in the HTLV negative group (P = 0.013). None of the patients with anticardiolipin antibodies exhibited venous thrombosis.

Subacute encephalomyelitis of AIDS and its relation to HTLV-III infection.

Subacute encephalitis, characterized by demyelination, gliosis of the gray and white matter, focal necrosis, microglial nodules, atypical oligodendrocyte nuclei, and multinucleation of cells, was present in 27 of 30 (90%) autopsied patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex. Subacute encephalitis was mainly distributed in the frontal (58%) and temporal (69%) lobes, basal ganglia (77%), amygdala (80%), and hippocampus (64%). Ten (37%) with moderate or severe subacute encephalitis were demented; 82% with mild subacute encephalitis had no recognized neurologic disorder. Human T-lymphotropic virus type III (HTLV-III) was isolated from neural tissue or CSF in 11 of 13 patients, 10 with subacute encephalitis, and 1 without CNS lesions. We conclude that subacute encephalitis is common in AIDS patients and is most likely caused by CNS infection with HTLV-III.

Neoplastic complications of HTLV-III infection. Lymphomas and solid tumors

Neoplastic disease arose in 29 of 200 patients infected with human T lymphotropic virus type III (HTLV-III) seen at a suburban hospital. Seventeen patients had Kaposi's sarcoma, one of whom also had colon carcinoma. Nine patients had lymphoproliferative disorders (seven lymphomas, one T suppressor cell chronic lymphocytic leukemia, and one multiple myeloma), including three with concomitant Kaposi's sarcoma and one with colon cancer. One other patient had colon cancer, one had a seminoma, and one had pancreatic cancer. Kaposi's sarcoma as a complication of AIDS occurred mainly in homosexuals (17 of 42 homosexuals, one of 17 drug abusers, one of five heterosexually promiscuous patients, and one of six patients who had previously received transfusions). The high-grade lymphomas did not show a predilection for any particular AIDS risk group. Three of four solid tumors arose in elderly AIDS patients. Twenty-five of 75 patients with CDC-defined AIDS had a neoplastic disorder (26 are still alive and may yet demonstrate malignancy). Few other diseases of man have been associated with as high an incidence of neoplastic transformation as occurs with HTLV-III infection.

Spectrum of HTLV‐III infection in a hemophilic cohort treated with blood products from a single manufacturer

One hundred fifty-eight hemophilia A, B, and von Willebrand disease (VWD) patients treated with clotting factor concentrates from a single manufacturer were tested for antibody to the human T-lymphotropic virus type III (HTLV-III). Antibody was detected in 63% and 40% of those with severe hemophilia A and B, respectively, 12% and 0% of those with mild hemophilia A and B, and two patients with recessive VWD. Forty-two antibody-positive and 20 antibody-negative patients were studied for clinical and laboratory features of infection. Eleven seropositive patients had clinical signs of infection including Pneumocystis carinii pneumonia, lymphadenopathy, splenomegaly or diarrhea; however, only one patient had developed acquired immune deficiency syndrome (AIDS), and only two had significant impairment of their performance status. Thirty-one patients remained totally asymptomatic. Eight patients had a history suggestive of acute HTLV-III infection. Thrombocytopenia was observed in 18% of seropositive patients, lymphopenia in 60%, depressed T-helper cells in 43%, reduced T-helper:T-suppressor ratios (TH:TS) in 33%, and elevated platelet-bound immunoglobulin in 53%. The antibody-negative group had normal T-helper cell levels (except one patient) and TH:TS ratios, and normal platelet immunoglobulin levels. Both groups demonstrated a significant elevation of immunoglobulin levels and a high prevalence of antinuclear factor and antismooth muscle antibodies. The mean level of IgG was significantly higher in the antibody-positive group. This study confirms the correlation between HTLV-III infection and reduced T-helper cells in hemophiliacs but demonstrates a low incidence of clinical symptomatology. There was evidence of polyclonal B-cell hyperactivity in the antibody-negative group as well as the seropositive group.

Children with AIDS.

The etiologic agent for acquired immune deficiency syndrome (AIDS) has been identified as human T lymphotropic virus type III (HTLV-III). Its distinguishing characteristics and putative receptor, the T4 molecule, are discussed. The Western Blot method has been applied to assess the presence of antibody to HTLV-III in patients as a measure of infection with HTLV-III. The definition of AIDS in children, based on the Centers for Disease Control surveillance criteria, is explored and expanded. Clinical and laboratory manifestations of pediatric AIDS are explained in the context of 'HTLV-III infection' through an analysis of prospective and retrospective serologic studies. Transmission of the disease is explored through parental history of infected children. Finally, the rationale for antibody replacement therapy is set forth.

Excretion of cytomegalovirus in semen associated with HTLV-III seropositivity in asymptomatic homosexual men.

We studied 56 asymptomatic homosexual male volunteers in Pittsburgh for 1 1/2 yr for relationships between cytomegalovirus (CMV) and human T-lymphotropic virus type III (HTLV-III) infections. CMV was most frequently isolated from semen (8%) as compared with throat washings (5.9%) and urine (0%) on initial testing of CMV-seropositive subjects. Other viruses commonly isolated from immunosuppressed patients (herpes simplex virus, adenovirus) were rarely detected in this cohort. Seropositivity to HTLV-III was significantly associated with isolation of CMV from semen in our asymptomatic cohort (odds ratio = 9.5, p = .008). These results suggest that HTLV-III infection is associated with selective, temporal activation of CMV in the genital tract of asymptomatic homosexual men.

Unusual features of scabies complicating human T-lymphotropic virus type III infection

Four cases of "exaggerated scabies" are described in patients who were immunodeficient secondary to human T-lymphotropic virus type III (HTLV-III) infection. As in classical scabies, these patients had a pruritic dermatitis but lacked the usual distribution of the eruption. The rash was initially misdiagnosed in all four patients. Scabies should be considered in pruritic dermatitis in patients at risk for HTLV-III infection.

Detection of antibodies to human T-lymphotropic virus type III by using a synthetic peptide of 21 amino acid residues corresponding to a highly antigenic segment of gp41 envelope protein.

A peptide of 21 amino acids with the sequence Arg-Ile-Leu-Ala-Val-Glu-Arg-Tyr-Leu-Lys-Asp-Gln-Gln-Leu-Leu-Gly-Ile-Trp- Gly-Cys - Ser encoded by a segment in the env gene of human T-lymphotropic virus type III (HTLV-III), corresponding to amino acids 586-606 of the precursor envelope glycoprotein, has been synthesized by the Merrifield solid-phase method. Combined serological and chemical analyses of this peptide and related peptides have revealed the importance of certain amino acid residues in the antigenic determinant of the relevant peptide. Enzyme immunoassay (EIA) employing this peptide as an antigen adsorbent was shown to reproducibly detect antibodies in sera of patients with HTLV-III infection. This assay provided positive results with all sera that were reactive with gp41 envelope protein of HTLV-III in electrophoretic immunoblot analysis. Thus far, no false-positive sera have been encountered in control populations. Our EIA with this peptide as the coating antigen is shown to have advantages over that with the whole HTLV-III virus as an immunoadsorbent.

The Walter Reed staging classification for HTLV-III/LAV infection.

Patients with acquired immunodeficiency syndrome (AIDS) represent a minority of those who have been infected with human T-lymphotropic virus type III (HTLV-III). The clinical presentation of patients with HTLV-III infections can range from asymptomatic through chronic generalized lymphadenopathy, to subclinical and clinical T-cell deficiency. The US Army has recently adopted a staging classification for HTLV-III infection. The purpose of the Walter Reed (WR) staging Classification is to provide uniformity for routine clinical evaluation of military personnel with HTLV-III infection, to facilitate understanding of the natural history of these infections, and to help evaluate the clinical response to antiviral treatment regimens. Stage WR0 designates high-risk contacts, while stages WR1-6 require documentation of HTLV-III infection. Stages WR1-6 show ascending degrees of disease, so that those classified in WR6 manifest antibodies to HTLV-III, chronic lymphadenopathy, T helper cell counts below the normal limit, delayed hypersensitivity, thrush, and opportunistic infection. HTLV-III infections with symptoms are designated by the addition of the letter B, while the occurrence of Kaposi's sarcoma is designated by adding the letter K. This classification scheme is based on the fact that the T helper cell is the principal target cell of HTLV-III and the clinical observation that the functional integrity of the T helper cell determines the clinical presentation. Preliminary studies in 39 sequential patients followed for over 18 months found that patients who entered in stages WR3-WR6 had a slow but progressive course to the next stage or death. Many questions about clinical progression remain, but it is hoped that this staging classification will facilitate their resolution.

Children with AIDS

The etiologic agent for acquired immune deficiency syndrome (AIDS) has been identified as human T lymphotropic virus type III (HTLV-III). Its distinguishing characteristics and putative receptor, the T4 molecule, are discussed. The Western Blot method has been applied to assess the presence of antibody to HTLV-III in patients as a measure of infection with HTLV-III. The definition of AIDS in children, based on the Centers for Disease Control surveillance criteria, is explored and expanded. Clinical and laboratory manifestations of pediatric AIDS are explained in the context of ‘HTLV-III infection’ through an analysis of prospective and retrospective serologic studies. Transmission of the disease is explored through parental history of infected children. Finally, the rationale for antibody replacement therapy is set forth.

Human T-cell growth factor (interleukin 2) and gamma-interferon genes: expression in human T-lymphotropic virus type III- and type I-infected cells.

Acquired immune deficiency syndrome (AIDS) is characterized by severe depletion of OKT4+ T lymphocytes and leukemia is associated with abnormal proliferation of maturation-arrested lymphocytes. Human T-lymphotropic virus type III (HTLV-III) or lymphoadenopathy virus (LAV) and type I (HTLV-I) are etiologically linked to AIDS and adult T-cell leukemia/lymphoma, respectively. T-cell growth factor (TCGF, also known as interleukin 2) is required for the growth of activated T-cells, which play an important role in immune regulation. gamma-Interferon (IFN-gamma) is also implicated in immune modulation. It was possible that T-cell depletion in acquired immune deficiency syndrome could be due to an impairment of TCGF synthesis and that adult T-cell leukemia could be due to unregulated production of TCGF. The results reported here show that the transcription of the TCGF gene was not impaired in cultured HTLV-III-infected cells. Paradoxically, the TCGF gene in HTLV-I-infected cells was transcriptionally inactive. The reverse was the case for the gamma-interferon gene--it was actively transcribed in HTLV-I-infected cells but not in the HTLV-III-infected and virus-producing H9 and H4 cell line. No evidence was obtained suggesting abnormal regulation of the TCGF or of the IFN-gamma gene consequent to HTLV-III infection. It thus appears that in both HTLV-III and HTLV-I infection, growth control and immune regulatory mechanisms may bypass a modulatory role of TCGF or of IFN-gamma.

Influence of the human T-lymphotropic virus/lymphadenopathy-associated virus on functions of human lymphocytes: evidence for immunosuppressive effects and polyclonal B-cell activation by banded viral preparations.

The etiologic agent for the acquired immunodeficiency syndrome (AIDS) is now firmly established as the retrovirus termed the human T-lymphotropic virus type III (HTLV-III) or the lymphadenopathy-associated virus, LAV. The disease is characterized by profound and progressive loss of immunity, but molecular evidence indicates that only a few cells in peripheral blood are being productively infected with this virus. In the present study we have investigated a disrupted HTLV-III viral preparation for biologic effects on normal lymphoid cells. Relatively dilute concentrations of this preparation were found to stimulate immunoglobulin secretion by peripheral blood lymphocytes; at the same dosages, the preparation was inhibitory for the B-cell differentiation responses that are induced with other known polyclonal B-cell activators, pokeweed mitogen, Staphylococcus aureus, and Epstein-Barr virus. This preparation was also inhibitory at high concentrations for T-lymphocyte proliferative responses to phytomitogens and antigens and resulted in a reduced expression of Tac antigen on phytohemagglutinin-activated lymphocytes. Paradoxically, incubation of lymphocytes of certain healthy donors with the HTLV-III preparation alone resulted in increased expression of Tac and Leu-12 antigens. These findings show that a disrupted preparation of HTLV-III virus can mimic many of the immunologic abnormalities present in patients with HTLV-III infection. Nonviable viral proteins may be responsible for some of the immunologic perturbations that occur in HTLV-III-infected states.

Antibody Seronegative Human T-Lymphotropic Virus Type III (HTLV-III)-Infected Patients With Acquired Immunodeficiency Syndrome or Related Disorders

AbstractThe 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.

Revision of the Case Definition of Acquired Immunodeficiency Syndrome for National Reporting—United States

The Conference of State and Territorial Epidemiologists (CSTE) approved the following definitions regarding the case definition of acquired immunodeficiency syndrome (AIDS) at its annual meeting in June 1985. 1st, the case definition of AIDS used for national reporting will continue to include only the more severe manifestations of human T-lymphotropic virus type III (HTLV-III) infection. 2nd, Centers for Disease Control (CDC) will develop more inclusive definitions and classifications of HTLV-III infection for diagnosis, treatment, and prevention, as well as for epidemiologic studies and special surveys. 3rd, a number of refinements will be adopted in the case definition of AIDS used for national reporting. In the absense of the opportunistic diseases required by the current case definition, disseminated histoplasmosis, isosporiasis, bronchial or pulmonary candidiasis, non-Hodgkin's lymphoma of high-grade pathologic type, and histologically confirmed Kaposi's sarcoma in patients 60 years or over will be considered indicative of AIDS if the patient has a positive serologic or virologic test for HTLV-III. Also, in the absence of the required opportunistic diseases, a histologically confirmed diagnosis of chronic lymphoid insterstitial pneumonitis in a child under 3 years of age will be considered indicative of AIDS unless HTLV-III antibody tests are negative. Patients who have a lymphoreticular malignancy diagnosed more than 3 months after the diagnosis of an opportunistic disease used as a marker for AIDS will no longer be excluded as AIDS cases. Finally, to increase the specificity of the case definition, patients will be excluded as AIDS cases if they have a negative result on testing for serum antibody to HTLV-III, have no other test for HTLV-III with a positive result, and do not have a low number of T-helper lymphocytes or a low T4:T8 ratio.

Antibody seronegative human T-lymphotropic virus type III (HTLV-III)- infected patients with acquired immunodeficiency syndrome or related disorders

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.

Seroepidemiology of human T-lymphotropic virus type III among homosexual men with the acquired immunodeficiency syndrome or generalized lymphadenopathy and among asymptomatic controls in Boston.

We studied a cohort of 45 homosexual men with the acquired immunodeficiency syndrome, 78 with persistent unexplained generalized lymphadenopathy, and 160 asymptomatic homosexual controls for serologic evidence of infection with human T-lymphotropic virus type III (HTLV-III). Study participants were recruited from a community-based health center and a university hospital practice. Ninety-eight percent of men with the syndrome and greater than 90% of men with generalized lymphadenopathy had antibody to HTLV-III, while 21% of the controls were positive (p less than 0.001). Six patients with generalized lymphadenopathy developed the acquired immunodeficiency syndrome over 2 years; all were seropositive for HTLV-III. Thirty-six asymptomatic controls had had sexual contact with a man with the syndrome; receptive anal intercourse in this group was associated with seropositivity for HTLV-III. These data suggest that persistent generalized lymphadenopathy and the acquired immunodeficiency syndrome are part of a clinical spectrum of HTLV-III infection and that most high-risk homosexual men in some regions of the United States have not yet been infected with this virus.

RECOMBINANT HUMAN INTERFERON ALFA-A SUPPRESSES HTLV-III REPLICATION IN VITRO

Recombinant human interferon alfa-A (rIFNαA) had a dose-related suppressive effect on human T lymphotropic virus type III (HTLV-III) replication in vitro in normal peripheral-blood mononuclear cells (PBMC). Both single-dose and multiple-dose regimens were inhibitory. Such inhibitory concentrations (4-1024 units/ml) were not toxic to PBMC in culture, and were within the ranges achievable in blood after injection. These studies suggest that clinical trials of rIFNαA in early HTLV-III infection are warranted.

NEEDLESTICK TRANSMISSION OF HTLV-III FROM A PATIENT INFECTED IN AFRICA

This article reports a case of needlestick transmission of human T-lymphotropic virus type III (HTLV-III) infection to a health care worker in the UK from a patient who was presumably infected while in Africa. The patient, a white woman who had lived in central southern Africa, presented at the hospital with general malaise, dry cough, and fever. Lung biopsy revealed Pneumocystis carinii pneumonia infection, and the patient was seropositive for HTLV-III infection with a titer of 260. The patient reported that she had been unwell for 2-3 years. She had none of the accepted risk factors for acquired immunodeficiency syndrome (AIDS), and neither she nor her husband had visited the US, the Caribbean, or Zaire. Serum from the husband was positive for HTLV-III antibodies at a titer of 450. Despite intensive management and treatment with pentamidine, the patient died. During management of this case, a nursing staff member sustained a needlestick injury to the finger while resheathing a hypodermic needle. A small amount of blood was probably injected. 13 days later, the health care worker developed a severe flu-like illness with sore throat, headache, myalgia, and facial neuralgia. A macular rash and generalized lymphadenopathy were also noted. Serum drawn 27 days after the incident was negative for anti-HTLV-III infection, but titers on days 49 and 57 were 12 and 24, respectively. This contrasts with experience in the US, where needlestick injuries in health care workers have not resulted in either disease or transmission. It is assumed that the patient acquired AIDS in Africa, and that the infection was transmitted heterosexually. This case raises the possibility of differences in infectivity and other characteristics between HTLV-III viruses of US and African origin.