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Biomedical subjects

A Gessain

Publications and source records attributed to A Gessain.

At least 109 records · Page 6Linked to original sources
PubMed1995

Human T-cell-leukemia virus type I in post-transfusional spastic paraparesis: complete proviral sequence from uncultured blood cells.

Human T-cell-leukemia virus type I (HTLV-I) is the causative agent of adult T-cell leukemia/lymphoma (ATL) and tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). The different disease outcome may be attributable to subtle mutations leading to modification of viral tropism or infectivity. Initial attempts found a very high level of sequence conservation among all HTLV-I strains. However, only one complete proviral DNA sequence is reported from a TSP/HAM patient, with a provirus derived from immortalized lymphocytes, which might be expected to be a leukemogenic variant rather than a neurotropic one. We cloned and sequenced a complete HTLV-I provirus (HTLV-IBoi) derived from the uncultured lymphocytes of a sub-acute post-transfusional TSP/HAM patient with clonal integration of HTLV-I. HTLV-IBoi proviral genome is 9033 bp long, and its overall genetic organization is similar to that of the prototype HTLV-I(ATK), without major deletions or insertions. No premature termination codon was found in the 4 open reading frames of the pX region. Divergence at the nucleotide level of HTLV-IBoi from the reported full-length HTLV-I varies from 1 to 9.4%, and indicates that it corresponds to a cosmopolitan genotype. This study did not identify specific sequences associated with neurotropic strains.

Adult↗
PubMed1995

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.

Adolescent↗
PubMed1995

Isolation and molecular characterization of a human T-cell lymphotropic virus type II (HTLV-II), subtype B, from a healthy Pygmy living in a remote area of Cameroon: an ancient origin for HTLV-II in Africa.

We report characterization of a human T-cell lymphotropic virus type II (HTLV-II) isolated from an interleukin 2-dependent CD8 T-cell line derived from peripheral blood mononuclear cells of a healthy, HTLV-II-seropositive female Bakola Pygmy, aged 59, living in a remote equatorial forest area in south Cameroon. This HTLLV-II isolate, designated PYGCAM-1, reacted in an indirect immunofluorescence assay with HTLV-II and HTLV-I polyclonal antibodies and with an HTLV-I/II gp46 monoclonal antibody but not with HTLV-I gag p19 or p24 monoclonal antibodies. The cell line produced HTLV-I/II p24 core antigen and retroviral particles. The entire env gene (1462 bp) and most of the long terminal repeat (715 bp) of the PYGCAM-1 provirus were amplified by the polymerase chain reaction using HTLV-II-specific primers. Comparison with the long terminal repeat and envelope sequences of prototype HTLV-II strains indicated that PYGCAM-1 belongs to the subtype B group, as it has only 0.5-2% nucleotide divergence from HTLV-II B strains. The finding of antibodies to HTLV-II in sera taken from the father of the woman in 1984 and from three unrelated members of the same population strongly suggests that PYGCAM-1 is a genuine HTLV-II that has been present in this isolated population for a long time. The low genetic divergence of this African isolate from American isolates raises questions about the genetic variability over time and the origin and dissemination of HTLV-II, hitherto considered to be predominantly a New World virus.

Adult↗
PubMed1995

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↗
PubMed1995

A new HTLV type II subtype A isolate in an HIV type 1-infected prostitute from Cameroon, Central Africa.

Among 332 female sex workers in Douala, Cameroon, 113 were HIV-1 seropositive, 3 were HTLV-I seropositive, and only 1 had specific anti-HTLV-II antibodies. By cocultivation with BJAB cells, an HTLV-II was isolated from the peripheral blood mononuclear cells of this 32-year-old woman coinfected by HIV-1. This new African HTLV-II isolate (PH230PCAM) belongs to the molecular subtype A, exhibiting, however, a nucleotide variability of 2.4% and 0.8%, vis-à-vis the MO prototype, in the LTR and in the gp21 env gene, respectively. These data, as well as the previous findings of another HTLV-II subtype A in a Ghanean prostitute, suggest that this viral subtype had been imported into Africa, while the HTLV-II subtype B, described in remote areas of Zaire, Gabon, and Cameroon, could be a genuine African HTLV-II, present in this continent for a long period of time.

Adult↗
PubMed1995

Isolation and characterization of a new simian T-cell leukemia virus type 1 from naturally infected celebes macaques (Macaca tonkeana): complete nucleotide sequence and phylogenetic relationship with the Australo-Melanesian human T-cell leukemia virus type 1.

A study of simian T-cell leukemia virus type 1 (STLV-1) infection in a captive colony of 23 Macaca tonkeana macaques indicated that 17 animals had high human T-cell leukemia virus type 1 (HTLV-1) antibody titers. Genealogical analysis suggested mainly a mother-to-offspring transmission of this STLV-1. Three long-term T-cell lines, established from peripheral blood mononuclear cell cultures from three STLV-1-seropositive monkeys, produced HTLV-1 Gag and Env antigens and retroviral particles. The first complete nucleotide sequence of an STLV-1 (9,025 bp), obtained for one of these isolates, indicated an overall genetic organization similar to that of HTLV-1 but with a nucleotide variability for the structural genes ranging from 7.8 to 13.1% compared with the HTLV-1 ATK and STLV-1 PTM3 Asian prototypes. The Tax and Rex regulatory proteins were well conserved, while the pX region, known to encode new proteins in HTLV-1 (open reading frames I and II), was more divergent than that in the ATK strain. Furthermore, a fragment of 522 bp of the gp21 env gene from uncultured peripheral blood mononuclear cell DNAs from five of the STLV-1-infected monkeys was sequenced. Phylogenetic trees constructed with the long terminal repeat and env (gp46 and gp21) regions demonstrated that this new STLV-1 occupies a unique position within the Asian STLV-1 and HTLV-1 isolates, being, by most analyses, related more to the Australo-Melanesian HTLV-1 topotype than to any other Asian STLV-1. These data raise new hypotheses on the possible interspecies viral transmission between monkeys carrying STLV-1 and early Australoid settlers, ancestors of the present day Australo-Melanesian inhabitants, during their migrations from the Southeast Asian land mass to the greater Australian continent.

Amino Acid Sequence↗
PubMed1994

Infection of rats with human T-cell leukemia virus type-I: susceptibility of inbred strains, antibody response and provirus location.

The susceptibilities of different strains of inbred rats to infection with the human T-cell leukemia virus (HTLV-I) after inoculation of human HTLV-I producer cell lines were compared. The Fisher F344 and Brown Norway strains developed the highest antibody response to HTLV-I, while the Lewis and BB strains were low responders. Antibodies against the HTLV-I gag proteins, and env gp21 but not env gp46, were detected in Western blots with sera from HTLV-I-infected Fischer F344 and Brown Norway rats. These sera were inactive in an in vitro syncytium-formation inhibition test. The HTLV-I provirus was detected by polymerase chain reaction in all Fischer F344, and some Lewis and Brown Norway rats, but not in the BB, which lack CD8+ T lymphocytes. The most frequent locations of the HTLV-I provirus in the Fischer F344, Lewis and Brown Norway rats at 12 weeks after infection were the peripheral blood mononuclear cells (PBMC) and spinal cord. In a second experiment in Brown Norway rats, the provirus was again detected in the PBMC of rats at 12 weeks, but not at 22 weeks, and among the other organs tested at 22 weeks the sympathetic nerve ganglia were positive. It is concluded that HTLV-I infection occurs in adult rats, but is suppressed with time.

Animals↗
PubMed1994

HTLV-I/II infection in a high viral endemic area of Zaire, Central Africa: comparative evaluation of serology, PCR, and significance of indeterminate western blot pattern.

The frequency of indeterminate Western blot (WB) seroreactivities against HTLV-I "gag encoded proteins" only, and the use of low specific diagnostic WB criteria led to the overestimation of HTLV-I seroprevalence in initial studies in intertropical Africa and Papua New Guinea. In order to clarify the meaning of such seroreactivity, 98 blood samples of individuals from a high HTLV-I endemic area in Zaire, Central Africa were studied by a WB assay containing HTLV-I disrupted virions enriched with a gp 21 recombinant protein and a synthetic peptide from the gp 46 region (MTA-1), and by the polymerase chain reaction (PCR) with 3 primers pairs and 4 different HTLV-I and or HTLV-II-specific probes. These 98 samples were taken mainly from patients with neurological diseases and from their relatives. Using stringent WB criteria, 28 sera (29%) were considered as HTLV-I-positive, 3 as negative and 67 (68%) as indeterminate. A large proportion of these indeterminate sera would have been considered as HTLV-I-positive samples according to previous low specific WB diagnostic criteria. After PCR, 35 samples (36%) were considered as positive for the presence of HTLV-I proviral DNA. Out of the 67 WB seroindeterminate, 10 (15%) were found HTLV-I-positive by PCR. These 10 individuals exhibited in WB multiple band reactivity with p19 and/or p24 (7 cases of both) associated in 6 cases with rgp 21, but never with MTA-1. No samples were found PCR-positive for HTLV-II despite the findings of 11 sera suggestive of HTLV-II by WB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Molecular epidemiology of HTLV type I in Japan: evidence for two distinct ancestral lineages with a particular geographical distribution.

Japan is one of the highest endemic areas of the world for human T cell leukemia-lymphoma virus type I (HTLV-I). To gain new insight as to the origin of this virus in Japan and especially in the southern islands of the archipelago, we investigated the long terminal repeat (LTR) of 67 newly isolated HTLV-I proviral DNAs from peripheral blood mononuclear cells of HTLV-I-infected individuals for their restriction fragment length polymorphism (RFLP). The specimens were from Japanese living in different geographical areas (Hokkaido, Honshu, Kyushu, or the Ryukyu Islands) of Japan (59 cases) or Americans of Japanese ancestry living in Hawaii (8 cases). The analysis of the results, together with data for the 19 previously published LTR sequences, demonstrated the existence of 2 subtypes of HTLV-I in Japan. The first, which we propose to name Japanese subtype (previously named subtype III), is more frequent (67 of 86: 78%) than the second, the cosmopolitan subtype (previously named subtype II) (19 of 86: 22%). In parallel, a fragment of 413 base pairs of the U3/R region (nucleotide 22 to 434) was cloned and sequenced from 10 of the new Japanese samples. The alignment of these sequences and their comparison and phylogenetic analysis with previously published LTR HTLV-I sequences, demonstrated clearly the existence of the two distinct molecular subtypes of HTLV-I in Japan, diverging in this LTR region by about 1.6%. Furthermore, the study of the geographical distribution of the 2 subtypes among the 80 samples from patients whose place of residence in Japan was known showed an uneven distribution. While the Japanese subtype was present in all parts of Japan, the cosmopolitan subtype seemed to cluster in the southern islands of the archipelago (i.e., Kyushu and the Ryukyu Islands) as well as in immigrants from those areas who had lived in Hawaii for decades. These new molecular data raise questions and suggest hypotheses, discussed here, concerning the origin and means of dissemination of these human retrovirus subtypes in Japan.

Adult↗
PubMed1994

Seroepidemiology, viral isolation, and molecular characterization of human T cell leukemia/lymphoma virus type I from La Réunion Island, Indian Ocean.

Data indicate the presence in the Seychelles Islands of a high level of human T cell leukemia/lymphoma virus type I (HTLV-I) endemicity as well as the presence of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). We present here the results of an hospital survey performed since 1988 in La Réunion Island, located in the Indian Ocean southeast of the Seychelles archipelago, aimed at evaluating HTLV-I endemicity, detecting HTLV-I-associated diseases, and characterizing viral isolates. Seven individuals were found to have HTLV-I-specific antibodies in their sera. These include 3 of 257 patients from St. Pierre Hospital, 1 of them exhibiting a typical clinical feature of TSP/HAM (the first described case in this region), 1 blood donor of 3900, and 3 relatives. A further nine individuals exhibiting only "gag-encoded proteins" by Western blot (p19 and/or p24 bands) were found negative by polymerase chain reaction using LTR, pol, and tax HTLV-I specific primers. A long-term T cell line, designated Mel.J, exhibiting T cell activation markers (CD4+, CD25+, HLA-DR+), and producing HTLV-I antigens and viral particles, was established from one of the HTLV-I,-seropositive patients. The sequence of a 522-bp fragment corresponding to the carboxy terminus of gp46 and the majority of gp21 were determined for five HTLV-I-seropositive individuals, including the TSP/HAM patient. Alignment and phylogenetic comparison of these five nucleotide sequences with all the 53 other available HTLV-I env sequences demonstrated that the virus from La Réunion Island belongs to the group of the HTLV-I cosmopolitan subtype and is not related to the Melanesian HTLV-I variants.

Adult↗