Severe Acquired Immunodeficiency in Male Homosexuals, Manifested by Chronic Perianal Ulcerative Herpes Simplex Lesions

616

193

By using in situ hybridization methodology, we have directly examined primary lymph node and peripheral blood from patients with acquired immunodefIciency syndrome (AIDS) and AIDS-related complex for the presence of human T-lymphotropic virus type M (HTLV-l) viral RNA. Mononuclear cell preparations were hybridized with a 35s labeled HTLV-II-specific RNA probe and exposed to autoradiographic emulsion for 2 days. HTLV-III-infected cells expressing viral RNA were detected in '86% (6/7) oflymph node and 50% (7/14) of peripheral blood samples studied. However, in all patient samples eained, labeled cells were observed at very low frequency (<0.01% of total mononuclear cells). The HTLV-II-infected cells exhibited morphological characteristics consistent with that of lymphocytes and expressed viral RNA at relatively low abundance (20-300 copies per cell).These results demonstrate that HTLV-lI expression in lymph node and peripheral blood is very low in vivo. Furthermore, the lymph node hyperplasia observed in HTLV-Il-associated lymphadenopathy is not directly due to proliferation of HTLVrn-infected lymphocytes.The acquired immunodeficiency syndrome (AIDS) presents a severe unexplained immune deficiency that involves reduction in the number ofhelper T lymphocytes (OKT4) (1-3). The disease is usually accompanied by multiple opportunistic infections and/or malignancies, the latter predominantly of the Kaposi sarcoma type (4). AIDS-related complex (ARC) encompasses milder forms and sometimes prodromal states of the disease, and it is characterized by other clinical manifestations, most frequently unexplained chronic lymphadenopathy or leukopenia involving helper T lymphocytes (1-4). Recent serologic and viral isolation studies have shown that the development of AIDS or ARC is due to infection with the human retrovirus, human T-cell lymphotropic virus type III (HTLV-III) (5-8). HTLV-III, a cytopathic virus, is included in the HTLV family because of multiple biological and structural properties in common with HTLV types I and II (reviewed in ref. 9), including: (i) tropism for lymphocytes; (ii) particular tropism for OKT4 helper T lymphocytes; (iii) magnesium-dependent reverse transcriptase of high molecular weight; (iv) induction of giant multinucleated cells in culture; (v) impairment of T-cell functions; (vi) immunological crossreactivity of some virally encoded proteins; (vii) double-spliced 3' terminal mRNA; (viii) relatively small major core protein (p24/p25); (ix) unique juxtaposition of p24/p25 to the NH2-terminal gag protein-i.e., absence of the gag gene-encoded phosphoprotein in this position; and (x) trans-acting transcriptional activity resulting from a specific protein encoded by a viral gene.By using cloned HTLV-III probes (10, 11), analysis of fresh tissue from AIDS and ARC patients was carried out for detection of viral sequences. Southern blot experiments detected HTLV-III viral DNA at low levels in fresh lymphoid tissue from a number, albeit a minority, ofpatients with AIDS or ARC (12). At the s...

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confidence: 99%

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confidence: 99%

Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization.

Harper¹,

Marselle²,

Gallo³

et al. 1986

616

193

“…Acquired immunodeficiency syndrome (AIDS) is associated with a retrovirus [lymphoadenopathy-associated virus (1), human T-cell leukemia virus type III (HTLV-III) (2), AIDSrelated virus (3)] that is cytotoxic for the OKT4+ subset (helper subset) of T cells and that apparently can result in a devastating series of opportunistic infections that are frequently fatal (4)(5)(6). The AIDS retrovirus can be transmitted in blood products such as donated whole blood (7) and factor VIII concentrates (8), so that methods to determine previous exposure of potential donors to the retrovirus are essential.…”

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confidence: 99%

Bacterial expression of the acquired immunodeficiency syndrome retrovirus p24 gag protein and its use as a diagnostic reagent.

Dowbenko¹,

Bell²,

Benton³

et al. 1985

A retrovirus [lymphoadenopathy-associated virus, human T-cell leukemia virus type III, acquired immunodeficiency syndrome (AIDS)-related virus] suspected of causing AIDS has been isolated recently. The detection of exposure to this retrovirus in donors of various blood products is important to prevent transmission of the disease from these donors to recipients. In the majority of cases, the detection of antibodies directed against either the viral core protein, a Mr approximately equal to 24,000 protein termed p24 gag, or the viral envelope antigen is proof of previous viral infection. Thus, we have expressed the p24 gag antigen in Escherichia coli in order to produce a diagnostic reagent for the detection of virus exposure. The bacterially synthesized antigen reacts with human and rabbit antisera directed against the native p24 gag protein in both electrophoretic transfer blot assay and ELISA. In addition, the use of bacterially produced antigens for ELISAs gave results that were comparable to those obtained by using antigens isolated from the virus.

“…In vitro, HTLV-I and HTLV-II infection transforms these T4 cells (14)(15)(16)(17), whereas infection with HTLV-III (or LAV) produces cytopathic effects and cell death (9,12). In vivo, the malignant cells from patients with ATLL and the patient with T-cell hairy cell leukemia are T4 cells (8,15,18,19), and in patients with fully developed AIDS the number of circulating T4 cells is profoundly reduced (20,21). However, it is not clear whether HTLV replicates primarily or exclusively in the T4 lymphocyte population.…”

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confidence: 99%

Infection of human endothelial cells by human T-cell leukemia virus type I.

Hoxie¹,

Matthews²,

Cines³

1984

130

The effects of the human T-cell leukemia virus type I (HTLV-I) on cultured human endothelial cells were evaluated. Coculture of endothelial monolayers with either irradiated HTLV-producing lymphocytes or cell-free virus resulted in the production of multinucleated syncytia. The development of syncytia was inhibited by sera from patients with adult T-cell leukemia/lymphoma (ATLL). HTLV antigens were present on endothelial syncytia passaged in culture for >3 months as detected by an anti-p19 monoclonal antibody, which detects a core protein of HTLV-I, and by ATLL sera. Moreover, these HTLV-infected endothelial cells were then able to infect and transform normal cord blood T lymphocytes with HTLV. These studies demonstrate that human endothelial cells are susceptible to productive HTLV-I infection in vitro and may have relevance for the spectrum of human disease associated with this family of retroviruses.