Human T-lymphotropic Retrovirus Type Research Articles

Proteomic analysis of plasma extracellular vesicles reveals mitochondrial stress upon HTLV-1 infection

Extracellular vesicles (EVs) can participate in intercellular communication and pathogenesis. EVs contain many cargos, including proteins, and the composition of EVs differs between cell-types and activation levels. Thus, plasma EVs can be used as a biomarker of systemic response to infection and/or disease progression. In this study, we aimed at describing alterations in the protein content of plasma EVs upon infection with the human T-lymphotropic retrovirus type 1 (HTLV-1). HTLV-1 is the etiological agent of a lymphoproliferative disease (ATL) and a series of inflammatory diseases, including a neurodegenerative inflammatory disease (HAM/TSP). We found that plasma EVs are more abundant and smaller in HTLV-1 asymptomatic carriers or HAM/TSP patients when compared to uninfected healthy donors. Moreover, EVs from HTLV-1 infected donors contain markers of metabolic and mitochondrial stress.

Paraparesia espástica tropical en un paciente con HTLV-I

The tropical spastic paraparesis associated to Human T-lymphotropic Retrovirus type 1 (HTLV-1) is a chronic, progressive myelopathy, characterized by bilateral involvement of the pyramidal tract with sphincter disorders. The main neuropathological features are chronic myelitis, perivascular injury, and parenchymal infiltration of the lymphocytes. A case is presented in this article and reviews the pathogeny, diagnosis and treatment of tropical spastic paraparesis.

Oncogenic DNA viruses.

The early discoveries of Gross (1951) of viral causation of murine leukemias, the subsequent demonstration of retroviruses as the causative factors and the presence of similar viruses particularly in lymphoproliferative disorders in cattle, cats, and various rodent species, underlined for decades the justi®cation of attempts to search for similar agents in human cancers, subsequently identi®ed as retroviruses. When Stehelin et al. (1976) proved the cellular origin of retroviral oncogenes, it appeared to be almost odd to search for agents who possess their own oncogenes and may be involved in human cancers. Yet, until today, with the exception of the human Tlymphotropic retrovirus type I as causative agent of adult T-cell leukemia, endemic in the coastal regions of southern Japan, di€erent groups of viruses emerged as prime factors even for some common human cancers. Besides Hepatitis C, they all contain DNA as genetic material and belong to very di€erent virus families. Roughly 15% of the global cancer burden can be linked to these infections. An additional 5% can be attributed to bacterial (Helicobacter pylori) and parasitic infections (Schistosoma, Opistorchis, Clonorchis). DNA virus types known to be involved in human cancers are listed in Table 1.

Viruses in human cancers

It has been one of the surprising aspects, particularly of the past 2 decades, that widespread chronic diseases, previously thought to be due to metabolic imbalances or genetic modifications, are increasingly linked to infectious events. Besides atherosclerosis, now suspected to be caused by chlamydial infections, approximately 15% of global cancer incidence is aetiologically related to specific infections. Bacteria (Helicobacter pylori) and helminths (Schistosoma, Opistorchis, Clonorchis) contribute to the development of gastric, bladder and rectal cancers and to cholangiocarcinomas. Viruses, however, emerge as major causal cancer factors. In addition to hepatocellular carcinomas, linked to hepatitis B and C virus infections, specific types of papillomaviruses have been shown to cause a major human cancer, cancer of the cervix. They have also been implicated in a number of other anogenital, oropharyngeal, and cutaneous cancers. Epstein–Barr virus (EBV), the longest known human tumour virus (since 1964), human herpes virus types 8 (HHV-8), and human T-lymphotropic retrovirus type 1 (HTLV-1) represent additional identified human tumour viruses.

Isolation of an HTLV-1-like retrovirus from patients with tropical spastic paraparesis.

Tropical spastic paraparesis (TSP) is a slowly progressive myelopathy associated with increased serum and cerebrospinal fluid antibodies to the human T-lymphotropic retrovirus type I (HTLV-I) (ref. 1), and has been observed in many regions of the world. A similar condition known as HTLV-I-associated myelopathy occurs in the Kagoshima prefecture of Japan. Recent but controversial reports suggest involvement of virus related to HTLV-I in multiple sclerosis. Magnetic resonance imaging and electrophysiological studies indicate that TSP lesions are like multiple sclerosis in that they are disseminated throughout the nervous system. Complete virus from patients with TSP has proved difficult to isolate using techniques successful in adult T-cell leukaemia cases associated with HTLV-I. Here we report the isolation of an HTLV-I-like virus from T-cell lines derived from the peripheral blood and cerebrospinal fluid of TSP patients. The monoclonal antibody OKT3 was used to generate non-transformed T-cell lines that express HTLV-I antigens. Infectious virus was demonstrated by co-cultivation and complete, replicating virions were visualized ultrastructurally.

Safe Disinfection of Contact Lenses After Contamination with HTLV-III

The human T-lymphotropic retrovirus type III (HTLV-III), the etiological agent of AIDS, has recently been detected in tears, cornea, and conjunctiva, raising the possibility of transmission of HTLV-III via contact lens trial sets used in routine fitting. We evaluated the ability of several contact lens cleaning solutions, with or without conditioning or disinfecting solutions, to disinfect contact lenses experimentally contaminated with HTLV-III. Following attempted disinfection, the lenses were cultured for residual HTLV-III on H9 cells for 28 days. Cultures without characteristic cytopathic effects, reverse transcriptase activity, and HTLV-III-specific antigen expression were considered negative. We found that all commercially available cleaning solutions tested were able to disinfect contact lenses exposed to HTLV-III.

Preferential transcription of HTLV-I LTR in cell-free extracts of human T cells producing HTLV-I viral proteins.

The promoters of the adenovirus 2 major late gene, the mouse beta-globin gene, the mouse immunoglobulin VH gene and the LTR of the human T-lymphotropic retrovirus type I were tested for their transcription activities in cell-free extracts of four cell lines; HeLa, CESS (Epstein-Barr virus-transformed human B cell line), MT-1 (HTLV-I-infected human T cell line without viral protein synthesis), and MT-2 (HTLV-I-infected human T cell line producing viral proteins). LTR was preferentially transcribed in the extracts of MT-2 although the other three genes were transcribed with relatively constant efficiencies in different extracts. The results agree well with the previous in vivo studies on the promoter activity of HTLV-I LTR. Mixing of HeLa and MT-2 extracts revealed the presence of a LTR-specific stimulating activity in MT-2 extracts.

Human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus antibody. Association with hemophiliacs' immune status and blood component usage

Human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus antibody. Association with hemophiliacs' immune status and blood component usage

Human T-Lymphotropic Retrovirus Type III / Lymphadenopathy-Associated Virus Antibody

We studied the human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody status of 234 factor VIII concentrate recipients, 36 factor IX concentrate recipients, 69 long-term recipients of frozen packed red blood cells, and 47 persons not receiving routine transfusion therapy. Factor VIII concentrate recipients had a significantly higher rate of seropositivity (74%) than any other group. Factor IX concentrate recipients had a significantly higher rate (39%) than recipients of frozen packed red blood cells (4%) or nontransfused persons (4%). In factor VIII concentrate recipients, HTLV-III/LAV seropositivity was significantly associated with more severe hemophilia, greater factor dosage, elevated immunoglobulin and immune complex levels, lower T-helper lymphocyte numbers, and lower ratios of T-helper to T-suppressor lymphocytes. For factor IX concentrate recipients, seropositivity was associated with more severe hemophilia. Antibody-positive factor IX concentrate recipients had a lower rate of seropositivity to HTLV-III/LAV p41 membrane antigen than did antibody-positive factor VIII concentrate recipients, but factor VIII and factor IX concentrate recipients had similar rates of seropositivity to core antigens. We conclude that both factor VIII and factor IX concentrates may transmit HTLV-III/LAV. For factor VIII recipients, HTLV-III/LAV seropositivity is associated with altered immune test results.

Human T-lymphotropic retrovirus type III (HTLV-III) in Danish homosexuals

Sera from 119 patients attending a venereal disease clinic in Copenhagen during May 1983 were screened for antibodies to the newly characterized and isolated retrovirus HTLV-III. Ten out of 45 (22%) homosexual patients and two out of 74 (2.7%) heterosexual patients were found to have antibodies against HTLV-III. The homosexual group (except one case that developed AIDS and died during one year observation period) contained otherwise healthy men some of which had no contact with individuals from high-risk areas and only a few sexual partners. These results strongly suggest that Danish homosexuals with only few contacts are also at risk and that sero-epidemiological studies should also include the healthy homosexual group and probably the heterosexual group attending venereal disease clinics.

A glycopolypeptide (gp 100) is the main antigen detected by HTLV-III antisera.

Sera from homosexuals and hemophiliacs in Germany were examined for antibodies to human T-lymphotropic retrovirus type III (HTLV-III) by an enzyme-linked immunosorbent assay (ELISA) against purified virus. ELISA positive sera were used to search by immunoprecipitation for HTLV-III related antigens in a persistently infected human T-cell line. A glycopolypeptide with a mol. wt. of 100 000 was regularly recognized by all positive sera. In analogy to glycosylation and high antigenicity of envelope polypeptides of other mammalian retroviruses, gp 100 seemed to be related to the env gen. Two polypeptides with mol. wts. of 24 000 and 22 000 probably representing viral core polypeptides were additionally detected by sera with high ELISA titers.

IgG antibodies to HTLV-III associated antigens in patients with AIDS and at risk for AIDS in The Netherlands.

Thirty-nine homosexual males, 11 of whom suffered from AIDS and 13 from Lymphadenopathy Syndrome (LAS), 18 healthy hemophiliacs and 12 healthy blood donors, not belonging to any AIDS risk group, were tested for IgG antibodies to Human T-lymphotropic retrovirus type III (HTLV-III) by indirect immunofluorescence. All tested people were from the area of Amsterdam or from elsewhere in The Netherlands. Five of 11 AIDS patients, 8 of 13 LAS patients and 5 of 15 healthy homosexuals had antibodies to HTLV-III. Five of 18 healthy hemophiliacs were seropositive for HTLV-III. None of the 12 blood donors was seropositive for HTLV-III.