Peripheral blood lymphocytes from patients with the acquired immunodeficiency syndrome (AIDS) or with signs or symptoms that frequently precede AIDS (pre-AIDS) were grown in vitro with added T-cell growth factor and assayed for the expression and release of human T-lymphotropic retroviruses (HTLV). Retroviruses belonging to the HTLV family and collectively designated HTLV-III were isolated from a total of 48 subjects including 18 of 21 patients wih pre-AIDS, three of four clinically normal mothers of juveniles with AIDS, 26 of 72 adult and juvenile patients with AIDS, and from one of 22 normal male homosexual subjects. No HTLV-III was detected in or isolated from 115 normal heterosexual subjects. The number of HTLV-III isolates reported here underestimates the true prevalence of the virus since many specimens were received in unsatisfactory condition. Other data show that serum samples from a high proportion of AIDS patients contain antibodies to HTLV-III. That these new isolates are members of the HTLV family but differ from the previous isolates known as HTLV-I and HTLV-II is indicated by their morphological, biological, and immunological characteristics. These results and those reported elsewhere in this issue suggest that HTLV-III may be the primary cause of AIDS.

https://science.sciencemag.org/content/sci/224/4648/500.full.pdf

Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS

A cell system was developed for the reproducible detection of human T-lymphotropic retroviruses (HTLV family) from patients with the acquired immunodeficiency syndrome (AIDS) or with signs or symptoms that frequently precede AIDS (pre-AIDS). The cells are specific clones from a permissive human neoplastic T-cell line. Some of the clones permanently grow and continuously produce large amounts of virus after infection with cytopathic (HTLV-III) variants of these viruses. One cytopathic effect of HTLV-III in this system is the arrangement of multiple nuclei in a characteristic ring formation in giant cells of the infected T-cell population. These structures can be used as an indicator to detect HTLV-III in clinical specimens. This system opens the way to the routine detection of HTLV-III and related cytopathic variants of HTLV in patients with AIDS or pre-AIDS and in healthy carriers, and it provides large amounts of virus for detailed molecular and immunological analyses.

https://science.sciencemag.org/content/sci/224/4648/497.full.pdf

Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDS

We constructed an infectious molecular clone of acquired immunodeficiency syndrome-associated retrovirus. Upon transfection, this clone directed the production of infectious virus particles in a wide variety of cells in addition to human T4 cells. The progeny, infectious virions, were synthesized in mouse, mink, monkey, and several human non-T cell lines, indicating the absence of any intracellular obstacle to viral RNA or protein production or assembly. During the course of these studies, a human colon carcinoma cell line, exquisitely sensitive to DNA transfection, was identified.

https://jvi.asm.org/content/jvi/59/2/284.full.pdf

Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone.

The complete nucleotide sequence of two human T-cell leukaemia type III (HTLV-III) proviral DNAs each have four long open reading frames, the first two corresponding to the gag and pol genes. The fourth open reading frame encodes two functional polypeptides, a large precursor of the major envelope glycoprotein and a smaller protein derived from the 3′-terminus long open reading frame analogous to the long open reading frame (lor) product of HTLV-I and -II.

Complete nucleotide sequence of the AIDS virus, HTLV-III

At a time when lesbian, gay, bisexual, and transgender individuals—often referred to under the umbrella acronym LGBT—are becoming more visible in society and more socially acknowledged, clinicians and researchers are faced with incomplete information about their health status. While LGBT populations often are combined as a single entity for research and advocacy purposes, each is a distinct population group with its own specific health needs. Furthermore, the experiences of LGBT individuals are not uniform and are shaped by factors of race, ethnicity, socioeconomic status, geographical location, and age, any of which can have an effect on health-related concerns and needs. While some research about the health of LGBT populations has been conducted, researchers still have a great deal to learn. To help assess the state of the science, the National Institutes of Health (NIH) asked the Institute of Medicine (IOM) to assess current knowledge of the health status of lesbian, gay, bisexual, and transgender populations; to identify research gaps and opportunities; and to outline a research agenda to help NIH focus its research in this area. A committee of experts was convened by the IOM to consider this task, and its findings are presented in its report, The Health of Lesbian, Gay, Bisexual, and Transgender People: Building a Foundation for Better Understanding.

The Health of Lesbian, Gay, Bisexual, and Transgender People: Building a Foundation for Better Understanding

Four previously healthy homosexual men contracted Pneumocystis carinii pneumonia, extensive mucosal candidiasis, and multiple viral infections. In three of the patients these infections followed prolonged fevers of unknown origin. In all four cytomegalovirus was recovered from secretions. Kaposi's sarcoma developed in one patient eight months after he presented with esophageal candidiasis. All patients were anergic and lymphopenic; they had no lymphocyte proliferative responses to soluble antigens, and their responses to phytohemagglutinin were markedly reduced. Monoclonal-antibody analysis of peripheral-blood T-cell subpopulations revealed virtual elimination of the Leu-3 / helper/inducer subset, an increased percentage of the Leu-2 + suppressor/cytoxic subset, and an increased percentage of cells bearing the thymocyte-associated antigen T10. The inversion of the T/ helper to suppressor/cytotoxic ratio suggested that cytomegalovirus infection was an important factor in the pathogenesis of the immunodeficient state. A high level of exposure of male homosexuals to cytomegalovirus-infected secretions may account for the occurrence of this immune deficiency.

Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency.

This article describes 5 cases of Pneumocystis carinii pneumonia occurring in homosexual men in Los Angeles California. All 5 patients had previous or current cytomegalovirus and candidal mucosal infection. The men 2 of whom have died ranged from 29-36 years of age. The patients did not know each other and had no known common contacts or knowledge of sexual partners with similar illnesses. The 5 did not have comparable histories of sexually transmitted disease. 4 had serologic evidence of past hepatitis B infection but no evidence of current hepatitis B surface antigen. 2 of the men reported frequent homosexual contact with various partners. All 5 reported use of inhalant drugs. The 3 patients in whom lymphocyte studies were performed had profoundly depressed in vitro proliferative responses to mitogens and antigens. The occurrence of pneumocystosis in these 5 previously healthy men without a clinically apparent underlying immunodeficiency is unusual but seems to reflect some association with a homosexual lifestyle or disease acquired through sexual contact. Cytomegalovirus infection has been shown to induce transient abnormalities of in vitro cellular immune function in healthy homosexual men with and without antibody and a high prevalence of cytomegalovirus infections has been reported among male homosexuals. In additon there is some evidence that seminal fluid may be an important vehicle of cytomegalovirus transmission. Although the role of cytomegalovirus infection in the pathogenesis of pneumocystosis reamins unknown the possibility of P. carinii infection should be carefully considered in previously healthy homosexuals with dyspnea and pneumonia.

J.D. Weisman

Papers

Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency.

Pneumocystis pneumonia--Los Angeles.

Pneumocystis Carinii Pneumonia and Mucosal Candidiasis in Previously Healthy Homosexual Men. Evidence of a New Acquired Cellular Immunodeficiency

Prophylaxis of Pneumocystis carinii infection in AIDS with pyrimethamine-sulfadoxine.