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PubMed1992

In vivo cellular tropism of human T cell leukemia virus type II (HTLV-II).

To investigate the in vivo cellular tropism of human T cell leukemia virus type II (HTLV-II), subpopulations of fresh peripheral blood mononuclear cells from infected individuals were isolated and analyzed by polymerase chain reaction for the presence of provirus. In eight of nine patients, HTLV-II was detected exclusively in the CD8+ T lymphocyte population. In the remaining patient, provirus was also detected in CD4+ T lymphocytes. Provirus was not detected in B lymphocytes or monocytes of any patient. These results suggest that in vivo HTLV-II has a preferential, and perhaps in some cases, an exclusive tropism for CD8+ T lymphocytes. The findings contrast sharply with those on HTLV-I where there is a preferential tropism for CD4+ T lymphocytes. Although HTLV-II infection has not been consistently associated with any lymphoproliferative disorders, the results suggest that if these occur, they may be different from those known to be associated with HTLV-I.

Adult↗
PubMed1992

Retrovirus infections in the south of Cameroon.

The results of a national HIV seroprevalence survey carried out in 1986/87 showed a 1% HIV seroprevalence in the South of Cameroon, which is higher than in the other regions of the country. We here demonstrate the presence of HTLV-I infections in the South of Cameroon with possible clustering of infection in some villages. Some evidence suggestive of the presence of HTLV-II was obtained. Sera from patients with onchocerciasis did not react on HTLV testing. No HTLV associated haematological or neurological syndromes were observed during this survey. Regarding the human immunodeficiency viruses, the HIV-1 prevalence varied from 0 to 3% in the different populations studied. None of the subjects was HIV-2 positive.

Blotting, Western↗
PubMed1992

Apparent ineffectiveness of natural killer cells vis-à-vis retrovirus-infected targets.

The role of NK cells in the defense against retroviral infections is ill defined. The discovery of the pathogenic human retroviruses and their epidemic spread have made more urgent a better understanding of how such infections may be naturally controlled. Therefore, a systematic study was undertaken to determine whether NK cells obtained from healthy individuals are able to recognize and lyse target cells that have been infected with HTLV-I, HTLV-II, or HIV. The studies demonstrated that NK cells can recognize retrovirus-infected cells as evidenced by rapid conjugation, but that neither freshly isolated, nor IL-2 stimulated cells cause lysis of such targets. As has been reported for NK-resistant tumor cells, removal of sialic acid residues rendered the retrovirus-infected target cells vulnerable to NK cell attack. Although these data do not suggest that boosting natural immunity would be a useful treatment modality for patients with AIDS or HTLV-related diseases, the observations may help to explain why the small number of cells that harbor retroviruses in patients with subclinical infection are not eliminated.

Cytotoxicity, Immunologic↗
PubMed1992

HIV and HTLV infections in 1305 transfusion-dependent thalassemics in Italy. The COOLEYCARE Cooperative Group.

OBJECTIVE: To evaluate the prevalence of antibodies to HIV-1/2 and HTLV-I/II in 1305 transfusion-dependent beta-thalassemics treated in 36 centres in Italy. DESIGN: Patient serum samples were collected during 1990 and tested in Milan. METHODS: Sera were screened using an enzyme-linked immunosorbent assay (ELISA) containing viral lysate antigens from HIV-1 and HIV-2, and a particle agglutination assay for the detection of antibodies to HTLV-I and HTLV-II. Repeatedly reactive samples were examined by Western blot (WB) assays containing recombinant and viral lysate antigens. Differential diagnosis was finally made by ELISA based on synthetic peptides. RESULTS: Samples from 36 of the 1305 patients (2.76%) contained anti-HIV-1 antibodies. In four patients seroconversion occurred after the implementation of anti-HIV-1 screening in blood donors in Italy (1985). Of the 36 HIV-1-antibody-positive samples, four were HIV-2 [corrected] WB indeterminate. These four samples were negative in assays based on specific synthetic peptides, suggesting cross-reactivity. Anti-HTLV-I antibodies were found in two patients from Sicily and one from Apulia, both southern Italian regions. Anti-HTLV-II antibodies were detected in another patient from Sicily. CONCLUSIONS: Antibodies to HIV-1, HIV-2, HTLV-I and HTLV-II were detected in 2.76, 0, 0.23 and 0.08% of patients, respectively. The residual risk of HIV-1 infection through blood transfusion after the implementation of anti-HIV-1 screening in blood donors in Italy was approximately 1:50,000 blood units; this is based on an approximate number of 200,000 blood units administered to our group of patients during 1986-1990 and the occurrence of four new anti-HIV-1 seroconversions. Seroconversions to HTLV-I/II suggest that these viruses are present in Italian blood donors.

Adolescent↗
PubMed1992

Detection of human T-cell leukemia/lymphoma virus, type II, in a patient with large granular lymphocyte leukemia.

We studied a patient with large granular lymphocyte (LGL) leukemia for evidence of human T-cell leukemia/lymphoma virus (HTLV) infection. Serum from this patient was positive for HTLV-I/II antibodies by enzyme-linked immunosorbent assay (ELISA) and was confirmed positive in Western blot and radioimmunoprecipitation assays. Results of a synthetic peptide-based ELISA showed that the seropositivity was caused by HTLV-II and not HTLV-I infection. Analyses of enzymatic amplification of DNA from bone marrow sections using the polymerase chain reaction (PCR) were positive for HTLV-II specific gag, pol, env, and pX gene sequences. Cloning and sequencing of amplified products showed that the HTLV-II pol and pX sequences in patient DNA differed from the sequences of 17 other HTLV-II isolates examined in our laboratory. HTLV infection may have a role in some patients in the pathogenesis of LGL leukemia.

Base Sequence↗
PubMed1992

Detection of HTLV-I in clinical specimens.

The American Red Cross, which collects 50% of blood for transfusion in the United States, now tests all prospective blood donors for HTLV-I and HTLV-II antibodies. It will therefore be important to recognize the significance and clinical spectrum of diseases associated with these viruses, and to become familiar with the current methods used to diagnose infection. This review summarizes the techniques currently in use to screen for HTLV-I/II antibodies, as well as methods to detect viral genome and/or gene products in blood and tissue specimens.

Deltaretrovirus Antigens↗
PubMed1992

Monoclonal antibodies and chemiluminescence immunoassay for detection of the surface protein of human T-cell lymphotropic virus.

Monoclonal antibodies (MAbs) raised against human T-cell lymphotropic virus type I (HTLV-I) recognized five distinct antigenic domains of viral env gene-encoded proteins. By using recombinant env proteins and synthetic peptides as mapping antigens, it was determined that the most immunogenic region represented a central portion of the retroviral surface protein (domain 2; amino acids 165 to 191). However, only a single MAb was able to react strongly with native viral proteins. This antibody (clone 6C2) was directed to an epitope within domain 4 (amino acids 210 to 306) of the retroviral env gene and reacted with envelope proteins in both HTLV-I and HTLV-II, as determined by immunoprecipitation, solid-phase binding, and immunoblotting. No reactivity against envelope components of other human retroviruses, including human immunodeficiency virus types 1 and 2, was present. Flow cytometry data demonstrated that MAb 6C2 reacted with cell lines chronically infected with HTLV-I or HTLV-II and also with surface antigens expressed on fresh adult T-cell leukemia cells, following up-regulation with interleukin-2. By a chemiluminescence immunoassay procedure, picogram amounts of viral surface protein could be detected in the unconcentrated supernatants of HTLV-infected cell lines and in diagnostic cultures. Levels of env and gag proteins released by cells into culture supernatants were not directly related to percent expression of cell surface viral-coat proteins. Further, the molar ratio of p19 to gp46 in conditioned media varied from strain to strain, possibly reflecting differences in viral assembly or packaging mechanisms. MAb 6C2 will be of value in characterizing the biochemical and immunological behavior of retroviral env gene proteins and in studying the interaction of HTLV-I and HTLV-II with their receptors.

Amino Acid Sequence↗
PubMed1992

Amplification and analysis of specific DNA and RNA sequences of bovine leukemia virus from infected cows by polymerase chain reaction.

Bovine leukemia virus (BLV) is the etiologic agent of leukemia in cattle and is believed to cause decreases in milk productivity, fertility, and life span in infected cows. BLV is a type C retrovirus in the Oncovirinae subfamily. It is most closely related to human T-cell lymphoma/leukemia virus type I (HTLV-I) and type II (HTLV-II). Since the polymerase chain reaction (PCR) provides rapid and efficient amplification of DNA sequences, primers were designed to amplify regions of the polymerase (pol) and pX genes specific for BLV targets. These sets of primers consistently amplified as few as 10 copies of BLV DNA contained in a plasmid in the background of 1 microgram of either human or bovine chromosomal DNA. In addition, no amplification products were detected from cell lines infected with HTLV-I, HTLV-II, or human immunodeficiency virus type 1 or 2 by the BLV PCR systems. Samples of peripheral blood mononuclear cells from 18 cows, previously determined to be serologically positive or negative, were correctly identified in a blind study as containing proviral DNA by use of the BLV primers and probes. Cloning and sequencing of amplified products revealed finite sequence variations among a previously cloned BLV isolate, the wild-type virus, and the published genome. Reverse transcriptase-directed PCR with the primers for both BLV pol and BLV pX was performed on plasma from a BLV-infected cow and detected in vivo BLV RNA expression. In summary, we have developed a specific and sensitive assay using PCR for the detection and identification of BLV infections; this assay can now be applied to clinical and basic research questions in veterinary medicine.

Animals↗
PubMed1992

[Chronic fatigue syndrome and virus infection: human herpesvirus 6 (HHV-6) infection].

Chronic fatigue syndrome (CFS) is newly-recognized disease characterized by chronic and debilitating fatigue. It has been suggested that viral infection may be involved in this syndrome from the results of clinical examination, including increased activity of 2',5'-synthetase in leukocytes of patients. The following viruses have been reported as etiologic agents of this disease. First, many studies have found elevated levels of IgG to viral capsid antigen and early antigens to Epstein-Barr virus (EBV), but low titer or absence of antibody to EBV-associated nuclear antigen. Second, the enteroviruses have also been implicated as possible causative agent of CFS, because virus could be isolated from patients. Recently it was also reported that antibodies to human T-lymphotropic virus (HTLV) and HTLV type II (HTLV-II) gag sequence were detectable in patients. Finally several reports state that human herpesvirus 6 (HHV-6) could be isolated from CFS patients in the high frequency. In conclusion, it is still early to identify the etiologic agent from these reports, and more effort is needed.

Fatigue Syndrome, Chronic↗
PubMed1992

Chronic leukaemias.

In recent years many subtypes of CLL and some CML variants have been recognized throughout the world by means of careful clinical, epidemiological, immunological, molecular biological and viral studies. Most striking has been the establishment of a close association between certain immunophenotypical subtypes of CLL and infection with HTLV-I and possibly HTLV-II. CLL has consistently been shown to have a strong genetic component and a low incidence among Asians, but a growing body of evidence also links this major leukaemia type with environmental factors including solvents, unidentified farming and other occupational exposures. In contrast, CML is characterized by few genetic associations, relatively homogenous world-wide distribution, greater frequency in Blacks than in Whites, little evidence of viral aetiology, and evidence that exposures to ionizing radiation, benzene and possibly other chemical agents are important aetiological factors. Most studies suggest that acquired rather than genetic factors are of greater importance in the aetiology of CML, but this conclusion is somewhat difficult to reconcile with the relatively small variation in incidence rates internationally. Common to both disorders in most populations are an increasing incidence with age, male predominance, and stability of incidence, survival and mortality over the years, exclusive of improved survival of CML following allogeneic bone marrow transplantation.

Adult↗
PubMed1992

Health care worker exposure to HIV-1 and HTLV I-II in critically ill, resuscitated emergency department patients.

STUDY OBJECTIVE: Exposure to HIV-1 is of profound concern to health care workers. HTLV-I and HTLV-II, retroviruses with similar modes of transmission as HIV-1, also cause disease in human beings. Emergency department resuscitations are high-risk situations for such exposure. The purpose was to determine the seroprevalence of HIV-1 and HTLV I-II in patients undergoing ED resuscitations, the magnitude of health care worker exposure, and risk factors associated with infection. DESIGN: Prospective identity-unlinked seroepidemiologic study. SETTING: ED of a 950-bed private inner-city teaching hospital. Participants included 370 patients undergoing ED resuscitations. MEASUREMENTS: Serum was tested for antibodies to HIV-1 and HTLV I-II. Questionnaires were completed by the physician in charge of the ED resuscitations. RESULTS: Fifteen (4.1%) (95% confidence interval [CI], 2.1% to 6.1%) patients were HIV-1 seropositive, and seven (1.9%) (95% CI, 0.7% to 3.1%) were HTLV I-II positive. Eleven (5.6%) (95% CI, 2.4% to 8.8%) of 197 trauma patients and 11 (6.4%) (95% CI, 2.8% to 10.0%) of 173 medical patients were infected with one of these viruses. Health care workers had direct cutaneous contact with patient blood during 114 (31%) ED resuscitations and with infected patient blood during 11 (3%) ED resuscitations. An additional 11 ED resuscitations involved parenteral exposures, one to HIV-1-infected blood. No factors could be identified that would quickly and reliably predict infection. CONCLUSION: Health care workers must protect themselves in such high-risk situations by strict compliance to mandatory universal precautions.

Adolescent↗
PubMed1992

No evidence for spumavirus or oncovirus infection in relapsing-remitting multiple sclerosis.

Polymerase chain reaction analysis was used to investigate the possible role of human spumaretrovirus and oncoretroviruses (human T-cell lymphotropic virus types I [HTLV-I] and II [HTLV-II]) in multiple sclerosis. Eleven patients with relapsing-remitting multiple sclerosis in exacerbation and 11 normal blood donors were included in the study. Cerebrospinal fluid cells, peripheral blood mononuclear cells, and plasma were cocultured with allogeneic mononuclear cells for 6 weeks. Cultured cells were subjected to polymerase chain reaction analysis with primers selected for the pol and gag (human spumaretrovirus), pol and env (HTLV-I), and pol (HTLV-II) genes. Polymerase chain reaction was negative in all patient and blood donor control samples, whereas positive controls were consistently reactive with high sensitivity. No culture exhibited cytopathic effects and supernatants were negative for reverse transcriptase activity. Thus, our results do not support a role for these retroviruses in the pathogenesis of multiple sclerosis.

Adult↗
PubMed1992

Simian T-cell leukemia virus type I infection in captive baboons.

Human T-cell leukemia virus type (HTLV-I) is a type C retrovirus that has been linked to both adult T-cell leukemia and neurological disorders in humans. Baboons and other Old World non-human primates harbor a related virus termed simian T-cell leukemia virus type 1 (STLV-I), which may also be associated with neoplastic disease. To explore the utility of the baboon as a model for HTLV-I infection and disease, 329 baboons from a colony of 3200 at the Southwest Foundation for Biomedical Research (SFBR) were analyzed for the presence of antibodies against STLV-I. An overall seroprevalence rate of > 40% was found, with higher rates in females versus males. Furthermore, seroprevalence rates increased dramatically with age, reaching greater than 80% in animals over the age of 16. Molecular and antigenic analysis of proviral DNA isolated from both tumor tissue and a cell line isolated from a baboon with non-Hodgkin's lymphoma (NHL) indicates that STLV-I in this colony is closely related to HTLV-I. Furthermore, monoclonally integrated provirus isolated from lymphoma tissue was detected, strongly implicating STLV-I in the etiology of this malignancy. DNA primer pairs homologous to HTLV-I sequences amplified both HTLV-I and STLV-I, but not HTLV-II, providing further evidence for a close genetic relationship between baboon-derived STLV-I and HTLV-I. The detailed study of a large population of naturally infected baboons may therefore shed some light into the complex processes required for the induction of disease associated with HTLV-I infection in humans.

Animals↗
PubMed1992

An antigenic structure of the trans-activator protein encoded by human T-cell leukemia virus type-I (HTLV-I), as defined by a panel of monoclonal antibodies.

In order to study an antigenic structure of the trans-activator protein encoded by human T-cell leukemia virus type-I (HTLV-I), tax1 antigen, we generated and characterized a panel of rat anti-tax1 monoclonal antibodies (MAbs) designated WATM-1, WATM-2, WATM-3, and WATM-4. These MAbs were derived from WKA rats immunized with HTLV-I-transformed (HTLV-I+) syngeneic T cells. Immunoblot assays showed that: (1) All the MAbs reacted with the tax1 antigen in HTLV-I+ cell lines and a recombinant tax1 antigen, PX141 (containing entire tax1 polypeptide); (2) WATM-3 and WATM-4, but not WATM-1 or WATM-2, reacted with a truncated tax1 antigen, XD59 (tax1 amino acids 180-338); (3) None of them reacted with another truncated tax1 antigen, XD128 (tax1 amino acids 1-47 and 286-353); and (4) each of the four MAbs had different reactivity with tax1-related antigens in the range 38-41 kDa expressed in simian cell lines infected with various HTLV-I-related simian retroviruses (STLV-I). None of the MAbs reacted with HTLV-II tax antigen. Human sera containing anti-tax1 antibodies interfered specifically with the antigen-specific binding of all the MAbs. These results suggest that the present rat MAbs are directed against various epitopes on the tax1 antigen. An antigenic structure of the tax1 antigen deduced from reactivity of a panel of anti-tax1 MAbs including the present rat MAbs is discussed.

Animals↗
PubMed1992

Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome.

BACKGROUND: The purpose of this study is to provide a case definition of chronic fatigue syndrome in an outbreak occurring in the Nevada-California region to evaluate candidate etiologic agents and observe the natural history of the illness. METHODS: Patients diagnosed as having chronic fatigue syndrome were studied by repeated interviews, questionnaires, and blood collection over a 3-year period. Serum samples were tested for antibodies to Epstein-Barr virus, human herpesvirus-6, and human T-lymphotropic viruses I and II. Leukocytes from typical cases were also assayed for human T-lymphotropic viruses I and II. RESULTS: Cases were defined as persons who had: (1) severe persistent fatigue following an acute illness appearing in an individual with no previous physical or psychological symptoms; (2) presenting signs and symptoms of an acute infection; (3) severe and persistent headache and/or myalgias; and (4) abrupt change in cognitive function or the appearance of a new mood disorder. After 3 years of follow-up, almost all study subjects were able to return to pre-illness activity. None of the viruses evaluated--human T-lymphotropic viruses I and II, Epstein-Barr virus, or human herpesvirus-6--could be etiologically linked to these outbreaks. CONCLUSION: Clinical features of outbreaks of chronic fatigue syndrome differ sufficiently to suggest different etiologic agents. Giardiasis appears to have precipitated one of the four clusters in this study but the cause(s) of the other three outbreaks is as yet uncertain. The overall prognosis of chronic fatigue syndrome is usually favorable.

Antibodies, Viral↗