Retrovirus particles with type C morphology were found in two T-cell lymphoblastoid cell lines, HUT 102 and CTCL-3, and in fresh peripheral blood lymphocytes obtained from a patient with a cutaneous T-cell lymphoma (mycosis fungoides). The cell lines continuously produce these viruses, which are collectively referred to as HTLV, strain CR(HTLVCR). Originally, the production of virus from HUT 102 cells required induction with 5-iodo-2′-deoxyuridine, but the cell line became a constitutive producer of virus at its 56th passage. Cell line CTCL-3 has been a constitutive producer of virus from its second passage in culture. Both mature and immature extracellular virus particles were seen in thin-section electron micrographs of fixed, pelleted cellular material; on occasion, typical type C budding virus particles were seen. No form of intracellular virus particle has been seen. Mature particles were 100-110 nm in diameter, consisted of an electron-dense core surrounded by an outer membrane separated by an electron-lucent region, banded at a density of 1.16 g/ml on a continuous 25-65% sucrose gradient, and contained 70S RNA and a DNA polymerase activity typical of viral reverse transcriptase (RT; RNA-dependent DNA nucleotidyltransferase). Under certain conditions of assay, HTLVCR RT showed cation preference for Mg2+ over Mn2+, distinct from the characteristics of cellular DNA polymerases purified from human lymphocytes and the RT from most type C viruses. Antibodies to cellular DNA polymerase γ and anti-bodies against RT purified from several animal retroviruses failed to detectably interact with HTLVCR RT under conditions that were positive for the respective homologous DNA polymerase, demonstrating a lack of close relationship of HTLVCR RT to cellular DNA polymerases γ or RT of these viruses. Six major proteins, with sizes of approximately 10,000, 13,000, 19,000, 24,000, 42,000, and 52,000 daltons, were apparent when doubly banded, disrupted HTLVCR particles were chromatographed on a NaDodSO4/polyacrylamide gel. The number of these particle-associated proteins is consistent with the expected proteins of a retrovirus, but the sizes of some are distinct from those of most known retroviruses of the primate subgroups.

https://www.pnas.org/content/pnas/77/12/7415.full.pdf

Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma

Acquired immune deficiency syndrome (AIDS) is characterized by opportunistic infections and by 'opportunistic neoplasms' (for example, Kaposi's sarcoma). Persistent generalized lymphadenopathy (PGL) is epidemiologically associated with AIDS, especially in male homosexuals. A subset of T lymphocytes positive for the CD4 antigen (also termed T4 antigen), is depleted in AIDS and PGL patients. A retrovirus found in T-cell cultures from these patients is strongly implicated in the aetiology of AIDS because of the high frequency of isolation and the prevalence of specific antibodies in the patients. Here we have detected cell-surface receptors for the AIDS retrovirus (human T-cell leukaemia virus-III (HTLV-III) and lymphadenopathy-associated virus-1 (LAV-1) isolates) by testing the susceptibility of cells to infection with pseudotypes of vesicular stomatitis virus bearing retroviral envelope antigens, and by the formation of multinucleated syncytia on mixing virus-producing cells with receptor-bearing cells. Receptors were present only on cells expressing CD4 antigen; among 155 monoclonal antibodies tested, each of the 14 anti-CD4 antibodies inhibited formation of syncytia and blocked pseudotypes. Productive infection of CD4+ cells with HTLV-III or LAV-1 markedly reduced cell-surface expression of CD4. In contrast, receptors for HTLV-I and HTLV-II were not restricted to CD4+ cells, were not blocked by anti-CD4 antibodies; cells productively infected with HTLV-I and HTLV-II expressed surface CD4. Hence, we conclude that the CD4 antigen is an essential and specific component of the receptor for the causative agent of AIDS.

The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus

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

1. Developmental Defects of the Oral and Maxillofacial Region 2. Abnormalities of Teeth 3. Pulpal and Periapical Disease 4. Periodontal Diseases 5. Bacterial Infections 6. Fungal and Protozoal Diseases 7. Viral Infections 8. Physical and Chemical Injuries 9. Allergies and Immunologic Diseases 10. Epithelial Pathology 11. Salivary Gland Pathology 12. Soft Tissue Tumors 13. Hematologic Disorders 14. Bone Pathology 15. Odontogenic Cysts and Tumors 16. Dermatologic Diseases 17. Oral Manifestations of Systemic Diseases 18. Facial Pain and Neuromuscular Diseases 19. Forensic Dentistry Appendix: Differential Diagnosis of Oral and Maxillofacial Diseases Part 1: Mucosal and Soft Tissue Pathology: Color Changes Part 2: Mucosal and Soft Tissue Pathology: Surface Alterations Part 3: Mucosal and Soft Tissue Pathology: Masses or Enlargements Part 4: Radiographic Pathology Part 5: Pathology of Teeth

Oral and Maxillofacial Pathology

Protection against intravenous simian immunodeficiency virus (SIV) challenge was assessed in rhesus macaques after immunization with a highly attenuated vaccinia (NYVAC)-SIV recombinant. One-third of vaccinated animals controlled viral infection and progressed to disease more slowly than control animals (Benson J, et al.: J Virol 1998;72:4170). However, this protection was not associated with neutralizing antibodies, cytotoxic T lymphocytes, or helper T cell responses. To explore other potential correlates of protection, we examined CD8+ T cell antiviral activity in macaques vaccinated with NYVAC-SIV, with or without added cytokine adjuvants, and in controls receiving only IL-12 or IL-12 plus IL-2. Before immunization, naive macaques exhibited a broad range of CD8+ T cell antiviral activity. Nevertheless, in the course of immunization, the vaccinated macaques as a group developed increased CD8+ T cell antiviral activity while the controls remained stable. Infectious SIV exposure also increased antiviral a...

CD8+ lymphocyte antiviral activity in monkeys immunized with SIV recombinant poxvirus vaccines: potential role in vaccine efficacy.

Oral delivery of replication-competent adenovirus vectors is well tolerated by SIV- and SHIV-infected rhesus macaques.

Polyvalent, primary isolate nucleic acid compositions for inducing an immune response against HIV is disclosed. The compositions and methods described herein are for the use of a DNA composition that encodes one or more different HIV envelope glycoproteins. The DNA composition can encode an HIV Gag protein. The DNAs encoding one or more HIV proteins are a combination of different nucleic acids, such as DNA plasmids, generated from primary isolate DNA of different HIV major group genetic clades and/or different proteins. HIV protein compositions for inducing an immune response against HIV are disclosed. Methods for using the protein compositions as boosts following administration of the DNA compositions are provided.

Polyvalent, primary hiv-1 glycoprotein dna vaccines and vaccination methods

This chapter reviews the events leading to the discovery of human T-lymphotropic virus type III (HTLV-III) the virus responsible for acquired immunodeficiency syndrome (AIDS). This virus shares many biologic and physiochemical properties common to the human T-cell leukemia viruses (HTLV) including tropism for T-lymphocytes induction of multinucleated giant cells a high molecular weight with a preference for reverse transciptase a relatively small major core protein (p24) distant antigenic and nucleic acid relatedness and a likely African origin. The frequent association of HTLV-III from patients with AIDS and AIDS-related complex (ARC) as well as the detection of antibodies specific for HTLV-III in nearly all patients with this disease leaves little doubt that HTLV-III is central to its etiology. This association was further confirmed by the detection of HTLV-III infection in hemophiliacs children with AIDS blood donors and previously healthy recipients of infected blood. Although the basic characterization of HTLV-III as a new retrovirus is now complete many question remain regarding its biologic and biochemical properties. Also unanswered is the fundamental question of how the virus exerts its cytopathic effects and causes AIDS. The nucleotide sequence analysis of HTLV-III which should be completed shortly should provide crucial information concerning the structural-functional relationships of the virus genome. This information along with expression studies and analyses of virus-specific proteins will be important to efforts to develop a vaccine against the virus. Also important will be the definition of the degree of genomic diversity that is present in HTLV-III and the determination of whether these differences have biologic significance.

Phillip D. Markham

Papers

CD8+ lymphocyte antiviral activity in monkeys immunized with SIV recombinant poxvirus vaccines: potential role in vaccine efficacy.

Oral delivery of replication-competent adenovirus vectors is well tolerated by SIV- and SHIV-infected rhesus macaques.

Polyvalent, primary hiv-1 glycoprotein dna vaccines and vaccination methods

The etiology of AIDS.

A Novel Epstein-Barr Virus-Like Virus, HVMNE, in aMacaca Nemestrina With Mycosis Fungoides