[Analysis of the ethical issues raised by a ten-year epidemiology program in French Guiana: limitations of the current legal framework and solutions adopted]. / Analyse des enjeux éthiques soulevés au cours d'un programme de recherche épidémiologique de dix années en Guyane française : limites de l'encadrement actuel et solutions adoptées.

BACKGROUND: This paper discusses the ethical aspects of a large research program in virology, conducted since 1994 and which has evolved in parallel with the elaboration of bioethics laws in France. This research, which involved the collection of a considerable amount of epidemiological data in the field, focused on epidemiological determinants (mother to child transmission, genetic susceptibility/resistance) of the human oncogenic retrovirus human T cell lymphotropic virus type 1 (HTLV-1). Data were collected from a specific population (Noirs Marrons) living in remote areas in French Guiana (South America). This ethnic group of African descent is highly endemic for HTLV-1 and associated adult T cell leukemia/lymphoma. The population has lived for two centuries on either side of the Maroni river, which constitutes the frontier between French Guiana and Surinam. The low socioeconomic and education levels of a large part of this population are mainly explained by a recent housing/residence fixation on the French side of the Maroni river. It is also linked to significant immigration from Surinam due to the civil war, which lasted for five years in the late 1990s, in this country. Conducting epidemiological surveys in this peculiar context illustrates the limitations of the available current legal framework in France for such studies. Indeed, several important ethical issues arose concerning not only individual and population benefits, but also specificities of the given information and of the informed consent. Another question concerns individual information feed-back in such a context of persistent viral infection, with a very low disease incidence, in a population with a relatively low education level. The goal of this work was mainly to report several of the ethical issues encountered and to discuss possible ways of achieving better information deliver and consent procedures in such a context. Indeed, these procedures should include new ideas and regulations promoting a real partnership, in order to conduct long-term epidemiological studies in populations with a low education level.

[HTLV1 infection and pregnancy]. / Infection par le rétrovirus HTLV-1 et grossesse.

OBJECTIVE: We report an epidemiological study with an analysis of the risk factors of the HTLV-1 seroprevalence in pregnant women and their children in the town of St Laurent du Maroni, French Guyana. MATERIAL AND METHOD: HTLV-1 seroprevalence and risk associated factors were first studied in all the pregnant women having delivered at St. Laurent between July 1991 and June 1993. Then, a retrospective analysis was performed in the children, aged between 18 months and 12 years old, born from HTLV-1 infected mothers, focusing especially on the duration of breast feeding and the level of HTLV-1 anti body titers and proviral load. RESULTS: The global HTLV-1 seroprevalence was 4.4% (75/1727) but it was more prevalent among ethnic groups of African origin such as the Noir Marron population (5.5%) and Haitians (6.3%). In the Noir-Marron population, which represents 70% of the studied population, HTLV-1 seropositivity was associated with a maternal age of>35 years, prior miscarriage, prior cesarean section, parity>4, gravidity>6 and negative rhesus factor. After logistic regression, HTLV-1 seropositivity remained associated with gravidity>6 and negative rhesus factor. Out of the 216 children born from 81 HTLV-1 infected mothers, only 21 were found to be HTLV-1 seropositive, giving a crude HTLV-1 transmission rate of 9.7% while among the 180 breast-fed children 10.6% were HTLV-1 seropositive. HTLV-1 seropositivity in children was associated with elevated maternal anti HTLV-1 antibody titer, high maternal HTLV-1 proviral load and child's gender, girls being more frequently HTLV-1 infected than boys. CONCLUSION: HTLV-1 infection, which can be responsible for severe pathologies in adults (adult T cell leukemia and tropical spastic paraparesis/HTLV-1 associated myelopathy) should be screened during pregnancy in women originating from high HTLV-1 endemic areas, as for France, mainly the French West Indies, French Guyana and Intertropical Africa. In case of HTLV-1 seropositivity, mothers should be informed on the risk of transmission and promotion of bottle feeding of their children should be strongly proposed.

Molecular characterization and phylogenetic analysis of a human T cell leukemia virus type 2 strain from French Guiana.

Extensive studies have been carried out on native Amerindian populations living in French Guiana in an attempt to detect human T cell leukemia virus type 2 (HTLV-2). However, the first strain of this virus identified in this region was not detected in these populations, but in a Brazilian woman of Amerindian origin. Comparative analyses of the nucleotide sequences of 589 bp of the gp21 env gene and of 625 bp of the long terminal repeat (LTR) showed that this new HTLV-2 strain (HTLV-2 GUY) was of subtype A. Sequence comparison and phylogenetic analyses demonstrated that HTLV-2 GUY was closely related to a group of distinct variants of HTLV-2 subtype A strains originating mostly from Brazilian inhabitants and formerly called HTLV-2 subtype C. As there is a high level of immigration from Brazil in French Guiana, we carried out a seroepidemiological study of 175 Brazilians, mostly women (obtained from a serum databank) and 72 female Brazilian prostitutes living in French Guiana to determine whether HTLV-2 is likely to become an emerging infection in this area. No HTLV-2 infection was detected, indicating that this virus is unlikely to become prevalent in the near future.

Serological, epidemiological, and molecular differences between human T-cell lymphotropic virus Type 1 (HTLV-1)-seropositive healthy carriers and persons with HTLV-I Gag indeterminate Western blot patterns from the Caribbean.

To investigate the significance of serological human T-cell lymphotropic virus type 1 (HLTV-1) Gag indeterminate Western blot (WB) patterns in the Caribbean, a 6-year (1993 to 1998) cross-sectional study was conducted with 37,724 blood donors from Guadeloupe (French West Indies), whose sera were routinely screened by enzyme immunoassay (EIA) for the presence of HTLV-1 and -2 antibodies. By using stringent WB criteria, 77 donors (0.20%) were confirmed HTLV-1 seropositive, whereas 150 (0.40%; P < 0.001) were considered HTLV seroindeterminate. Among them, 41.3% (62) exhibited a typical HTLV-1 Gag indeterminate profile (HGIP). Furthermore 76 (50.7%) out of the 150 HTLV-seroindeterminate subjects were sequentially retested, with a mean duration of follow-up of 18.3 months (range, 1 to 70 months). Of these, 55 (72.4%) were still EIA positive and maintained the same WB profile whereas the others became EIA negative. This follow-up survey included 33 persons with an HGIP. Twenty-three of them (69.7%) had profiles that did not evolve over time. Moreover, no case of HTLV-1 seroconversion could be documented over time by studying such sequential samples. HTLV-1 seroprevalence was characterized by an age-dependent curve, a uniform excess in females, a significant relation with hepatitis B core (HBc) antibodies, and a microcluster distribution along the Atlantic coast of Guadeloupe. In contrast, the persons with an HGIP were significantly younger, had a 1:1 sex ratio, did not present any association with HBc antibodies, and were not clustered along the Atlantic façade. These divergent epidemiological features, together with discordant serological screening test results for subjects with HGIP and with the lack of HTLV-1 proviral sequences detected by PCR in their peripheral blood mononuclear cell DNA, strongly suggest that an HGIP does not reflect true HTLV-1 infection. In regard to these data, healthy blood donors with HGIP should be reassured that they are unlikely to be infected with HTLV-1 or HTLV-2.

Human herpesvirus 8 transmission from mother to child and between siblings in an endemic population.

BACKGROUND: Transmission of human herpesvirus 8 (HHV-8), the aetiological agent of Kaposi's sarcoma, is known to occur during sex among homosexual men. However, other modes of HHV-8 transmission remain to be elucidated in endemic populations. METHODS: We did a population-based seroepidemiological survey in a village in French Guiana among 1337 individuals of African origin (age 2-91 years) who had reliable genealogical data. Plasma samples were taken and tested for HHV-specific IgG by immunofluorescence assay. Risk factors and familial correlations for HHV-8 seropositivity were modelled by logistic regression analysis by use of the estimating equations approach, which expresses familial dependences in terms of odds ratios. Familial odds ratios were also acquired by use of the distribution of all possible pairs of a given familial dependence. FINDINGS: The overall HHV-8 seroprevalence was 13.2% with no difference according to sex. HHV-8 seropositivity was strongly age dependent: at 1.2% under 5 years, HHV-8 seroprevalence rose up to a plateau around 15% between 15 and 40 years, and showed a seroprevalence of more than 27% in individuals older than 40 years. Strong familial aggregation in HHV-8 seroprevalence was found with high mother-child (odd ratio 2.8 [95% CI 1.6-5.0]) and sib-sib (3.8 [1.6-9.5]) correlations. By contrast, no significant correlation between spouses (0.6 [0.2-1.9]) was seen. INTERPRETATION: This pattern of familial aggregation, together with the variation of HHV-8 seroprevalence with age, indicate that, in endemic populations, HHV-8 transmission mainly occurs from mother to child and between siblings during childhood and adolescence.

Decrease of human T-cell lymphotropic virus type I prevalence and low incidence among pregnant women from a high endemic ethnic group in French Guiana.

To assess the prevalence and incidence of human T-cell lymphotropic virus type I (HTLV-I), 4,234 pregnant women of different ethnic origins were tested before each delivery between 1991 and 1997 in a high HTLV-I endemic area of French Guiana. HTLV-I was significantly more prevalent among ethnic groups of African descent as the Noir-Marrons (4.8%, 95% confidence interval [CI]: 4.0-5.6) and Haitians (5%, 95% CI 1.6-8.4). An age dependence of HTLV-I seroprevalence was observed. The mean age of Noir-Marron HTLV-I seronegative women was lower than for HTLV-I seropositive women (24. 7 vs. 28.6, p < 0.001). A decline in HTLV-I seroprevalence was observed, particularly in the Noir-Marron younger than 21 years old (p = 0.04). For five HTLV-I seroconversions observed, the incidence per 100 women-years in the Noir-Marron group was 0.19 (95% CI 0.02-0. 35) for all women, 0.32 in those 25 years old or younger (95% CI 0-0. 64), and 0.07 in those older than 25 years (95% CI 0-0.2). This observation was inconsistent with HTLV-I seroprevalence observed for those 25 years old or younger (2.8%) and those older than 25 (8.3%). These data demonstrate, for the first time outside Japan, a birth cohort effect for HTLV-I in a highly endemic ethnic group.

Detection of a major gene predisposing to human T lymphotropic virus type I infection in children among an endemic population of African origin.

Human T lymphotropic virus type I (HTLV-I) is a human oncoretrovirus that causes an adult T cell leukemia/lymphoma and a chronic neuromyelopathy. To investigate whether familial aggregation of HTLV-I infection (as determined by specific seropositive status) could be explained in part by genetic factors, we conducted a large genetic epidemiological survey in an HTLV-I-endemic population of African origin from French Guiana. All of the families in 2 villages were included, representing 83 pedigrees with 1638 subjects, of whom 165 (10.1%) were HTLV-I seropositive. The results of segregation analysis are consistent with the presence of a dominant major gene predisposing to HTLV-I infection, in addition to the expected familial correlations (mother-offspring, spouse-spouse) due to the virus transmission routes. Under this genetic model, approximately 1. 5% of the population is predicted to be highly predisposed to HTLV-I infection, and almost all seropositive children <10 years of age are genetic cases, whereas most HTLV-I seropositive adults are sporadic cases.

Detection and genetic polymorphism of human herpes virus type 8 in endemic or epidemic Kaposi's sarcoma from West and Central Africa, and South America.

Kaposi's-sarcoma-associated herpesvirus(KSHV)/human-herpes-virus-8(HHV-8) sequences originally detected in AIDS-associated Kaposi's sarcoma have been found in almost every KS tested, whether endemic, classic, iatrogenic or epidemic. Most of the studies on African KS involved East African patients. We report herewith the study of 17 African or Guyanan KS patients, 3 with epidemic KS (EKS) from Central African Republic, 3 from Senegal (2 EKS and 1 endemic KS), 3 EKS from Cameroon and 8 from French Guiana (3 EKS and 5 endemic KS). Serum-specific antibodies directed against latent and/or lytic HHV-8 antigens were present in 16 of them (94%), detected either by immunofluorescence assay and/or by immunoperoxidase. Polymerase chain reaction (PCR), using specific primers for HHV-8 ORF26 (233 bp) and ORF75 (601 bp), was carried out on DNA extracted from KS cutaneous biopsies, clinically uninvolved skin biopsies and peripheral-blood mononuclear cells (PBMC). HHV-8 DNA was detected in 16 out of 16 (100%) KS biopsies, regardless of their origin or clinico-pathological sub-type, in 7 out of 15 (47%) normal skin samples and 7 out of 16 (44%) PBMC. Comparative PCR, carried out in 7 patients, regularly found a much higher viral load in KS biopsies than in autologous normal skin and PBMC samples. Sequencing of fragments of the ORF26 and of the ORF75 demonstrated that the 16 HHV-8 strains were of the A, B or C sub-type. Furthermore, sequences of the entire ORF K1 of 4 strains showed that these HHV-8 strains of African origin were of the A5 or the B sub-type.

Mother-to-child transmission of human T-cell-leukemia/lymphoma virus type I: implication of high antiviral antibody titer and high proviral load in carrier mothers.

In order to gain new insights into the risk factors influencing human-T-cell-leukemia/lymphoma-virus-type-I (HTLV-I) mother-to-child transmission, a retrospective study of HTLV-I infection among children born to HTLV-I-seropositive women was carried out in a highly HTLV-I-endemic population of African origin living in French Guyana. The study covered 81 HTLV-I-seropositive mothers and their 216 children aged between 18 months old and 12 years old. All plasma samples were tested for the presence of HTLV-I antibodies by ELISA, immunofluorescence assay and Western blot. HTLV-I provirus was detected, in the DNA extracted from peripheral-blood mononuclear cells, by polymerase chain reaction (PCR) using primers specific for 3 different HTLV-I genomic regions (LTR, gag and pX) and quantified by a competitive PCR assay. Out of the 216 children, 21 were found to be HTLV-I-seropositive, giving a crude HTLV-I transmission rate of 9.7%, while among the 180 breast-fed children 10.6% were HTLV-I-seropositive. Perfect concordance between serological and PCR results was observed, and none of the 195 HTLV-I-negative children was found HTLV-I-positive by PCR. In conditional (by family) logistic-regression models, HTLV-I seropositivity in children was associated with an elevated maternal anti-HTLV-I-antibody titer (OR 2.2, p = 0.0013), a high maternal HTLV-I proviral load (OR 2.6, p = 0.033) and child's gender, girls being more frequently HTLV-I-infected than boys: OR 3.6, p = 0.0077 in the model including maternal anti-HTLV-I-antibody titer and OR 4.1, p = 0.002 in the model including the maternal HTLV-I proviral load.

Seroepidemiological and molecular studies of human T cell lymphotropic virus type II, subtype b, in isolated groups of Mataco and Toba Indians of northern Argentina.

We studied plasma samples from 2082 Mataco Indians living in 22 different communities in the western part of Formosa Province, northern Argentina. Samples were screened for HTLV-I/II antibodies by particle agglutination assay. All positive or borderline samples were then tested by an immunofluorescence assay (IFA) on C19 HTLV-II-producing cells. Western blot was used for confirmation of all IFA-positive plasma samples. The crude HTLV-II seroprevalence was 3.0% (62 of 2051), and 0.9% (5 of 588) in children less than 10 years old. The latter result suggests ongoing mother-to-child transmission, probably by breast feeding. There was a marked increase in HTLV-II seroprevalence with age (0.9%, 0-10 years; 1.6%, 11-20 years; 4.4%, 21-30 years; 3.4%, 31-40 years; 7.2%, 41-50 years; 5.7%, >50 years) in both male (p = 0.002) and female subjects (p = 0.00002). None of the 80 non-Indian inhabitants tested was HTLV-I/II seropositive. In a second study, among 105 Toba Indians from a village (Primavera) of the eastern part of this region, 23 were HTLV-II seropositive with a seroprevalence of 59% in those more than 40 years old. From seven of the Indians from Primavera, three others from neighboring regions (including two Tobas and one Pilaga), and one intravenous drug user (IVDU) from Rosario, DNA was extracted from peripheral blood mononuclear cells, and the gp21 transmembrane-encoding gene (590 bp) was amplified by PCR, cloned, and sequenced. LTR sequences were also obtained from the Pilaga, the IVDU, and one Toba. Molecular and phylogenetic analyses revealed that the Indians were all infected with closely related HTLV-II molecular strains belonging to the b subtype, while the IVDU was infected with an HTLV-II subtype a variant. Such data help to make a phylogenetic atlas of HTLV-II among Amerindian tribes and are crucial to gain new insights into the origin and modes of dissemination of this human retrovirus in the Americas.

Demographic and familial characteristics of HTLV-1 infection among an isolated, highly endemic population of African origin in French Guiana.

To determine the epidemiological characteristics of human T cell leukemia/lymphoma virus type I (HTLV-I) infection in the endemic village of Maripasoula, French Guiana, 1,614 persons (83.2% of the population) aged 2 to 91 years (mean age 21) were studied from November 1994 through April 1995. Plasma samples were screened by an HTLV-I ELISA and an IFA test (on MT2 cells), and positive samples were tested by an HTLV-I and -II type-specific Western blot. Overall seropositivity in the village was 6.7%, but HTLV-I infection was restricted to 3 of 6 ethnic groups, including the Noir-Marron (descendants of escaped African slaves, 8%), the Creoles (4.1%) and those of mixed Noir Marron/other ethnicity (3.6%). In the Noir-Marron population of 1,222 persons, including 606 men and 616 women and representing 76% of those tested, HTLV-I seroprevalence increased significantly with age in both sexes, reaching 40% in women older than 50 years. Univariate risk factors for HTLV-I seropositivity in women included older age, more pregnancies, more live births and a history of hospitalization. A cross-sectional analysis of sexual partners demonstrated an excess of discordant female HTLV-I+/male HTLV-I- couples, indicating preferential male-to-female sexual transmission. The demonstration of II HTLV-I-seropositive children aged less than 15 years, of whom 9 had a seropositive mother, suggested maternal-child HTLV-I transmission. Our results demonstrate a very high seroprevalence of HTLV-I in this South American population descended from African slaves, probably due to high rates of mother-to-child and sexual transmission within this rather isolated group.

[Molecular characterization of HTLV-II from an intravenous drug addict with AIDS in Argentina]. / Caracterización molecular de HTLV-II de un paciente drogadicto endovenoso con SIDA de la Argentina.

Ten intravenous drug user AIDS patients were studied to determine the presence of HTLV-I/II infection. Sera were screened by particle agglutination test and by an in house indirect immunofluorescence assay using MT2 (HTLV-I) and C19 (HTLV-II) producing cell lines. Out of the ten sera, one was confirmed HTLV-II positive by Western blot. Peripheral blood mononuclear cells were obtained from this patient, separated through a Ficoll-Hypaque gradient and DNA was extracted and amplified by semi-nested PCR. The amplified product obtained was cloned and sequenced. Results demonstrated the presence of HTLV-II proviral DNA and comparison of the obtained sequence with different HTLV-II prototypes led to classify the virus into subtype a. This is the first molecular characterization of HTLV-II in an intravenous drug user in Argentina.

Quantification of HTLV-II proviral copies by competitive polymerase chain reaction in peripheral blood mononuclear cells of Italian injecting drug users, central Africans, and Amerindians.

To better correlate the burden of human T cell leukemia virus type I (HTLV-I) and type II (HTLV-II) infection with diagnostic and prognostic markers, we developed a new competitive polymerase chain reaction (PCR) assay for the quantitative determination of proviral copy numbers in infected cells. A competitive plasmid was constructed that carried a 112-bp fragment from a highly conserved region of the HTLV tax gene and that was further modified by inserting a sequence of 24 bp. This competitive PCR assay system can be used for the quantification of HTLV-I and HTLV-II proviral DNA as demonstrated by using HTLV-I- and HTLV-II-infected cell lines and/or patient material. We determined the HTLV-II proviral load in peripheral blood mononuclear cells (PBMCs) of 11 Italian injecting drug users (IDUs) infected by this virus and in PBMCs of 10 seropositive Amerindian and Central African individuals from endemically infected ethnic groups. A great variation was observed in the number of HTLV-II proviral sequences in the PBMCs of Italian drug abusers, ranging from 5-10 to 16,239 copies/10(5) cells. There was no clear-cut correlation between proviral load, CD8 count, stage of HIV-1 infection, and therapy. A considerable variation in HTLV-II proviral load was also observed in PBMCs of Amerindians and Central Africans with no correlation between the amount of HTLV-II provirus and the geographic origin of the infected individuals.

Risk factors for maternal HTLV-I infection in French Guiana: high HTLV-I prevalence in the Noir Marron population.

The aim of this study was to compare rates of human T-cell lymphotropic virus type I (HTLV-I) seroprevalence in pregnant women belonging to different ethnic groups in French Guiana and to determine the risk factors associated with HTLV-I seropositivity. All 1,873 deliveries between 1 July 1991 and 30 June 1993 in the only gynecologic and obstetric unit at Saint Laurent du Maroni were enrolled. Serologic status could be established for 1,727 women, with 75 (4.3%) being HTLV-I seropositive. The HTLV-I seroprevalence rate differed significantly between ethnic groups: 5.7% for Noir-Marron (70/1,302), 6.3% for Haitian (3/50), and 0% for Creole (126), Amerindians (166), and Hmong (64). In Noir-Marron pregnant women, HTLV-I seropositivity was associated with a maternal age of > 35 years [odds ratio (OR), 3.3; 95% confidence interval (CI), 1.4-7.6], prior miscarriage (OR, 1.7; CI, 1-2.8), prior cesarean section (OR, 2.1; CI, 1.1-4.0), a parity > 4 (OR, 4.0; CI, 1.8-8.8), a gravidity > 6 (OR, 4.2; CI, 2.0-7.2), and a negative Rhesus factor (OR, 2.2; CI, 1.1-4.5). Two separate stepwise logistic regressions were done because gravidity and parity were highly correlated. HTLV-I seropositivity remained associated with a gravidity > 6 (OR, 3.9; CI, 2.1-7.4) and a negative Rhesus factor (OR, 2.6; CI, 1.2-5.3) for the first model and with a parity > 4 (OR, 4.1; CI, 1.9-9.0) and a negative Rhesus factor (OR, 2.5; CI, 1.2-5.1) for the second model.(ABSTRACT TRUNCATED AT 250 WORDS)

[Adult T-cell leukemia and non-malignant adenopathies associated with HTLV I virus. Apropos of 17 patients born in the Caribbean region and Africa]. / Leucémies à cellules T de l'adulte et adénopathies non malignes associées au virus HTLV I. A propos de 17 malades originaires des Caraïbes et d'Afrique.

Adult T-cell leukaemia is the first blood disease caused by a retrovirus: HTLV-1. The authors report the first French series of 15 patients, of whom 9 came from the classical endemic areas--the Antilles and outer Caribbean Islands--and 6 from Africa where the serological prevalence of HTLV-1 is high but few cases of adult T-cell leukaemia have been reported. Emphasis is laid on the importance of immunodeficiency (refractory strongyloidiasis, Pneumocystis carinii pneumonia, polyclonal B lymphoproliferative syndrome) and of other pathologies associated with the retrovirus (polyarthritis, lymphocytic interstitial pneumonia). The authors also describe the presence of adenopathy in healthy carriers: either adenitis suggestive of retroviral infection, or Castelman's disease adenopathy. These clinical presentations are similar to those described in lymphadenopathy syndromes due to the human immunodeficiency viruses. Aggressive lymphomas require chemotherapy, but sooner or later resistance develops, and the prognosis is very poor. The indications for allogeneic bone marrow transplantation are still to be determined. The diagnosis of adult T-cell leukaemia must be considered in all patients with blood disease coming from the endemic areas.

Cell surface phenotype and human T lymphotropic virus type 1 antigen expression in 12 T cell lines derived from peripheral blood and cerebrospinal fluid of West Indian, Guyanese and African patients with tropical spastic paraparesis.

Twelve long-term cell lines were established from peripheral blood mononuclear cells (PBMC) or cerebrospinal fluid cells of patients with human T lymphotropic virus type I (HTLV-1) seropositive tropical spastic paraparesis (TSP) originating from the French West Indies, French Guyana or the Central African Republic. Most of these long-term interleukin-2-dependent cell lines exhibited a pattern characteristic of CD4(+)-activated T cells with high expression of CD2, CD3 and CD4 antigens, associated with a strong density of TAC and DR molecules. Nevertheless, in five cases CD8 expression was present at a significant level. HTLV-I antigens were never detected in uncultured PBMC, but they were expressed in a few cells after short-term culture and after 4 months the majority of the cells were HTLV-I positive, as demonstrated by indirect immunofluorescence (IF) using polyclonal or monoclonal anti-p19 and anti-p24 antibodies. Low and variable levels of reverse transcriptase activity were detected in supernatant fluids of these cell lines only after 4 months of culture, when at least 50% of the cells exhibited HTLV-I antigens by IF. However, numerous type C HTLV-I-like viral particles were detected, mostly in the extracellular spaces, with rare budding particles. Similar findings were found in three T cell lines derived from West Indian and African patients with adult T-cell leukaemia/lymphoma (ATLL). Differences in high Mr polypeptides were detected by Western blot in cell lysates when comparing TSP- or ATLL-derived T cell lines. Thus a signal of 62K was easily detectable in all the TSP lines, but not in the ATLL lines. In all cell lines bands corresponding to p53, p24 and p19 viral core polypeptides were present, as was the env gene-coded protein p46.

High human T-cell lymphotropic virus type I proviral DNA load with polyclonal integration in peripheral blood mononuclear cells of French West Indian, Guianese, and African patients with tropical spastic paraparesis.

Human T-cell lymphotropic virus type I (HTLV-I) proviral integration status was examined by Southern blot analysis in peripheral blood mononuclear cell (PBMC) DNA from patients presenting a tropical spastic paraparesis (TSP) and serological evidence of HTLV-I infection. Surface phenotype and morphological aspects of PBMC were also studied. A polyclonal HTLV-I proviral integration was found in the PBMC of the 10 patients studied irrespective of their geographical origin (French West Indies, French Guiana, and Africa), the duration of their clinical illness, or the HTLV-I antibody titer. Furthermore, by dilution experiments and hypothesizing that only one copy of HTLV-I proviral DNA is present in one cell, we estimated that this HTLV-I integration is present in 3% to 15% of their PBMC. All 10 TSP/HTLV-I patients studied had an average of 10% of their lymphocytes abnormal, presenting either a misshapen nucleus or an adult T-cell leukemia/lymphoma (ATL)-like feature. Moreover, an elevated CD4/CD8 ratio associated with the presence of activated T cells with a high level of DR expression was observed in most patients. The significant frequency of viral-positive PBMC and the important load of HTLV-I proviral DNA that we observed in TSP/HTLV-I patients might play an important role in the pathogenesis of this recently identified clinico-virological entity.