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A Gessain

Publications and source records attributed to A Gessain.

At least 91 records · Page 5Linked to original sources
PubMed1997

Molecular epidemiology of 58 new African human T-cell leukemia virus type 1 (HTLV-1) strains: identification of a new and distinct HTLV-1 molecular subtype in Central Africa and in Pygmies.

To gain new insights on the origin, evolution, and modes of dissemination of human T-cell leukemia virus type I (HTLV-1), we performed a molecular analysis of 58 new African HTLV-1 strains (18 from West Africa, 36 from Central Africa, and 4 from South Africa) originating from 13 countries. Of particular interest were eight strains from Pygmies of remote areas of Cameroon and the Central African Republic (CAR), considered to be the oldest inhabitants of these regions. Eight long-term activated T-cell lines producing HTLV-1 gag and env antigens were established from peripheral blood mononuclear cell cultures of HTLV-1 seropositive individuals, including three from Pygmies. A fragment of the env gene encompassing most of the gp21 transmembrane region was sequenced for the 58 new strains, while the complete long terminal repeat (LTR) region was sequenced for 9 strains, including 4 from Pygmies. Comparative sequence analyses and phylogenetic studies performed on both the env and LTR regions by the neighbor-joining and DNA parsimony methods demonstrated that all 22 strains from West and South Africa belong to the widespread cosmopolitan subtype (also called HTLV-1 subtype A). Within or alongside the previously described Zairian cluster (HTLV-1 subtype B), we discovered a number of new HTLV-1 variants forming different subgroups corresponding mainly to the geographical origins of the infected persons, Cameroon, Gabon, and Zaire. Six of the eight Pygmy strains clustered together within this Central African subtype, suggesting a common origin. Furthermore, three new strains (two originating from Pygmies from Cameroon and the CAR, respectively, and one from a Gabonese individual) were particularly divergent and formed a distinct new phylogenetic cluster, characterized by specific mutations and occupying in most analyses a unique phylogenetic position between the large Central African genotype (HTLV-1 subtype B) and the Melanesian subtype (HTLV-1 subtype C). We have tentatively named this new HTLV-1 genotype HTLV-1 subtype D. While the HTLV-1 subtype D strains were not closely related to any known African strain of simian T-cell leukemia virus type 1 (STLV-1), other Pygmy strains and some of the new Cameroonian and Gabonese HTLV-1 strains were very similar (>98% nucleotide identity) to chimpanzee STLV-1 strains, reinforcing the hypothesis of interspecies transmission between humans and monkeys in Central Africa.

Africa, Central↗
PubMed1997

Molecular characterization and phylogenetic analyses of a new, highly divergent simian T-cell lymphotropic virus type 1 (STLV-1marc1) in Macaca arctoides.

A serological survey of a captive colony of Asian monkeys indicated that six Macaca arctoides had antibodies to human T-cell leukemia/lymphotropic viruses (HTLV). Over a 4-year interval, sera from these animals continued to exhibit a peculiar Western blot (WB) pattern resembling an HTLV-2 pattern (p24gag reactivity of equal or greater intensity than that of p19gag and a strong reactivity to recombinant gp21) but also exhibiting, in five of six cases, a reactivity against MTA-1, an HTLV-1 gp46 peptide. PCR experiments on DNA extracted from peripheral blood mononuclear cells using HTLV-1- or HTLV-2-specific long terminal repeat, gag, pol, env, and tax primers yielded negative results. However, highly conserved primers successfully amplified three different gene segments of env, tax, and env-tax. The results of comparative sequence analysis demonstrated that STLV-1marc1 was not closely related to any known STLV-1 strain, was the most divergent strain of the HTLV-1-STLV-1 group, and lacked the ATG initiation codons corresponding to the p12 and p13 proteins of HTLV-1. Phylogenetic analyses incorporating representative strains of all known HTLV-STLV clades consistently depicted STLV-1marc1 within the HTLV-1-STLV-1 type 1 lineage, but it probably diverged early, since its position is clearly different from all known viral strains of this group and it had a bootstrap resampling value of 100%. Genetic distance estimates between STLV-1marc1 and all other type 1 viruses were of the same order of magnitude as those between STLV-2PanP and all other type 2 viruses. In light of the recent demonstration of interspecies transmission of some STLV-1 strains, our results suggest the existence in Asia of HTLV-1 strains related to this new divergent STLV-1marc1 strain, which may be derived from a common ancestor early in the evolution of the type 1 viruses and could be therefore considered a prototype of a new HTLV-STLV clade.

Animals↗
PubMed1996

Adult T-cell leukemia/lymphoma on a background of clonally expanding human T-cell leukemia virus type-1-positive cells.

Tumorous and nontumorous samples from patients with various forms of adult T-cell leukemia/lymphoma (ATLL) were analyzed using the sensitive inverse polymerase chain reaction (PCR) technique. In all samples, oligoclonal expansion of human T-cell leukemia virus (HTLV)-1 bearing T cells were detected, even for the tumorous samples that were mainly monoclonal by Southern blotting. For one case of smouldering ATLL, chemotherapy apparently reduced the number of detectable clones. Taken together with similar data on asymptomatic and symptomatic HTLV-1 carriers without malignancy, it would appear that ATLL appears on a prior background of HTLV-1-initiated oligoclonal expansion.

Adult↗
PubMed1996

Clonal expansion of human T-cell leukemia virus type II in patients with high proviral load.

In previous studies we demonstrated that individuals infected by human T-cell leukemia virus type II (HTLV-II) presented a high degree of variation in proviral load and that the cellular tropism of this virus was expanded in some patients to B-lymphocytes. To understand whether the observed high proviral load could be associated with the clonal expansion of the infected cells, we have studied the mode of integration of HTLV-II in six infected individuals with proviral load higher than 1% of total peripheral blood mononuclear cells (PBMCs). An inverse polymerase chain reaction (PCR) analysis, which allowed the amplification of the region flanking the 5' end of the provirus, was developed for HTLV-II. A single band, corresponding to a monoclonal expansion, was found in four of six patients analyzed, while in the other two patients an oligoclonal type of integration was observed. The results for inverse PCR analysis were confirmed by sequencing the PCR products and showing that the 5' LTR flanking sequences of proviral DNA obtained from the different subjects presented no homology, thus suggesting that no specific site or sequence is required for the integration process of HTLV-II. The results indicate that the HTLV-II high proviral load observed in PBMCs from infected patients is associated with a clonal expansion of HTLV-II-infected cells. This study also suggests that the very high genetic stability of HTLV-II could be explained by viral amplification via clonal expansion rather than by reverse transcription.

Blotting, Southern↗
PubMed1996

Proliferation of HTLV-1 infected circulating cells in vivo in all asymptomatic carriers and patients with TSP/HAM.

Assuming that the clonal expansion of T cells harbouring the human T-cell leukemia virus type 1 (HTLV-1) provirus is a central feature of HTLV-1 infection, the identification of such cells was sought among a series of 19 asymptomatic carriers and 19 cases of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) devoid of malignancy. Two PCR based protocols designed to amplify the host cell-HTLV-1 proviral integration sites were used. In all cases large numbers of proliferating clones could be identified. The proportion of some clones was > 1/1500 peripheral blood mononuclear cells (PBMCs) with the suggestion that their number increased as a function of age among asymptomatic carriers.

Adult↗
PubMed1996

Evidence in Gabon for an intrafamilial clustering with mother-to-child and sexual transmission of a new molecular variant of human T-lymphotropic virus type-II subtype B.

Following the observation of an HTLV-II seropositive 60-year-old woman living in Gabon (Central Africa), a serologic and molecular study of her family members was conducted in an attempt to determine the duration of the HTLV-II infection and the modes of transmission of the virus. Among 41 family members, five were HTLV-I seropositive and 7 exhibited specific HTLV-II antibodies in their sera as demonstrated by high immunofluorescence titers on C19 cells and/or specific Western-blot pattern. The second husband of the index case and two of his sisters were infected by the virus, suggesting the presence of HTLV-II in this family over two generations. Sequence analysis of an amplified fragment of 172 nucleotides within the gp21 of the env region (6469-6640) of four HTLV-II infected individuals revealed a new HTLV-II molecular variant of the subtype b diverging from the prototypes NRA and G12 by seven (4.1%) and five (2.9%) bases substitutions, respectively. Molecular analysis of the total env gene (1462 bp) and fragments of the pol and pX regions confirmed that this new African variant was the most divergent HTLV-II subtype b yet described, exhibiting 2.3% of nucleotide substitutions in the env gene (33 bases) as compared to the two HTLV-II b prototypes. These data demonstrate, for the first time in Africa, intrafamilial both mother-to-child transmission and sexual transmission between spouses of an HTLV-II b molecular variant, and also suggest that this virus has been present in Gabon for a long period of time.

Adult↗
PubMed1996

Tropical spastic paraparesis/HTLV-I-associated myelopathy in Europe and in Africa: clinical and epidemiologic aspects.

We review here the epidemiologic and clinical aspects of tropical spastic paraparesis, human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (TSP/HAM) as observed in Europe and in Africa. Europe is not an endemic region for HTLV-I (seroprevalence in blood donors, < 0.03%), and TSP/HAM is thus rarely observed in European countries. Most of the few patients suffering from TSP/HAM are first- or second-generation immigrants from HTLV-I endemic areas (mostly the West Indies), and the clinicoepidemiologic aspects of these patients are similar to those seen in endemic areas. However, rare cases occur in European-born subjects with or without risk factors for HTLV-I infection, which raises the possibility of limited foci areas in Europe. Although Africa is considered as a primary HTLV-I endemic area, with at least a few million infected inhabitants, epidemiologic data on the situation of TSP/HAM in Africa remain scarce. Relatively few cases of patients with TSP/HAM have been reported in Africa, including some clusters in Zaire (prevalence, 50/100,000) and in South Africa and sporadically in the main cities of some Western, Central, and Eastern African countries. The paucity of clinical and epidemiologic data on TSP/HAM may be linked to several factors, including the paucity of neurologists, the lack of laboratory and radiologic facilities, and the chronicity of the disease, along with the limited number of field epidemiologic studies performed on this topic and the wide diversity of causes (toxic, nutritional, and infectious) of chronic myelopathies as seen on the African continent.

Adolescent↗
PubMed1996

Clonal expansion of infected cells: a way of life for HTLV-I.

Human T-cell lymphotropic virus type I (HTLV-I) is characterized by a remarkable genetic stability and high proviral loads in the absence of malignant disease. This results from the effect of tax on cell cycling. The virus replicates essentially in concert with the cell that is, via mitosis, which can be shown by polymerase chain reaction amplification of the HTLV-I integration sites. This is true of all stages of HTLV-I infection and accompanies adult T-cell leukemia/lymphoma. The very low viremia results from its genetic organization.

Cell Division↗
PubMed1996

Genetic variability and molecular epidemiology of human and simian T cell leukemia/lymphoma virus type I.

In the past few years, numerous investigators have demonstrated that human T cell leukemia/lymphoma virus type I (HTLV-I) possesses a great genetic stability, and recent data indicate that viral amplification via clonal expansion of infected cells, rather than by reverse transcription, could explain this remarkable genetic stability. In parallel, the molecular epidemiology of HTLV-I proviruses showed that the few nucleotide changes observed between isolates were specific for the geographical origin of the patients but not for the type of the associated pathologies (adult T cell leukemia/lymphoma, tropical spastic paraparesis/HTLV-I-associated myelopathy). Thus, based on sequence and/or restriction fragment length polymorphism analysis of more than 250 HTLV-I isolates originating from the main viral endemic areas, three major molecular geographical subtypes (or genotypes) emerged, strongly supported by phylogenetic analysis (high bootstrap values). Each of these genotypes (Cosmopolitan, Central African, and Melanesian) appeared to arise from ancient interspecies transmission between monkeys infected with simian T cell leukemia/lymphoma virus type I and humans. Furthermore, careful sequences analyses indicate that, within (or alongside) these three main genotypes, there are molecular subgroups defined clearly by several specific mutations but not always supported by phylogenetic analyses. Thus in Japan, there is evidence for two ancestral HTLV-I lineages: the classical Cosmopolitan genotype, representing approximately 25% of the HTLV-I present in Japan and clustering in the southern islands; and a related subgroup that we called the Japanese group. Similarly, within the Central African cluster, there are molecular subgroups defined by specific substitutions in either the env or the long terminal repeat. Furthermore, recent data from our laboratory indicate the presence of a new molecular phylogenetic group (fourth genotype) found among inhabitants of Central Africa, particularly in Pygmies. While geographical subtypes vary from 2 to 8% between themselves, HTLV-I quasi-species present within an individual appear to be much lower, with a variability of < 0.5%.

Africa↗
PubMed1996

What is the situation of human T cell lymphotropic virus type II (HTLV-II) in Africa? Origin and dissemination of genomic subtypes.

Human T cell lymphotropic virus type II (HTLV-II) and its two genomic subtypes, A and B, which differ by 3 to 6% at the nucleotide level (depending on the gene studied), were until recently considered to be endemic only in certain Indian tribes in the Americas and were therefore considered mainly as a "New World virus." First, the evidence of HTLV-II antibodies and later characterization of isolates from sex workers or individuals living in large West and Central African cities suggested that HTLV-II subtype A could have been imported recently in Africa. However, the findings of HTLV-II infection in two Pygmy populations living in remote areas of Zaire and Cameroon suggest that HTLV-II might have been in Africa for a very long time. Furthermore, the discovery of HTLV-II subtype B virus in some of these Pygmies, but also in other individuals from Zaire and within a family in Gabon for three generations, confirms the hypothesis of a very ancient presence of this HTLV-II subtype B on the African continent Recent data indicate also that there exist in Central Africa specific HTLV-II divergent strains including an HTLV-II B variant strain in Gabon. In the context of recent evidence for interspecies transmission in Central and West Africa of HTLV-I/simian T cell lymphotropic virus type I (STLV-I) strains, leading to the two major HTLV-I African subtypes, we would like to suggest that some STLV-II (closely related to HTLV-II subtype B) still exist or might have existed in Central/East Africa. The recent finding of quite divergent primate T cell lymphotropic viruses (PTLVs) in several Pygmy chimpanzees of Zairian origin (PTLV-PP1664 and STLV-PP) and in wild-caught baboons in Eritrea, Ethiopia (PTLV-L), also supports the complementary hypothesis of a yet to be discovered new HTLV-II-related virus in humans. Careful study of the indeterminate Western blot patterns present in some populations in Central Africa strongly suggests that such an exciting possibility exists, thus opening new avenues of research on both the history of primate retroviruses and that of early human groups.

Adolescent↗
PubMed1996

Virological aspects of tropical spastic paraparesis/HTLV-I associated myelopathy and HTLV-I infection.

TSP/HAM, a chronic spastic paraparesis or paraplegia with sphincter disturbances and minimal sensory loss, is characterized pathologically by a meningo-myelitis of the lower thoracic cord with axonal degeneration and demyelinisation of the lateral and anterior spinal tracts. High titer specific anti HTLV-I antibody is present in the serum and in the cerebrospinal fluid with specific intrathecal IgG synthesis, elevated IgG index and intra blood-brain barrier IgG synthesis. Most TSP/HAM patients also exhibit IgG oligoclonal bands in the CSF (also sometimes in the serum), some of those being HTLV-I specific, directed against p24 or against various antigens of the disrupted virus. HTLV-I specific cytotoxic T lymphocytes (CTL), mainly CD8+HLA class I restricted, and recognizing several HTLV-I epitopes especially of the tax, the rex and env proteins are present at high levels in the blood and CSF of TSP/HAM patients. These findings of high CTL activity have led some authors to suggest that these specific CD8 cells may play a major role in TSP/HAM pathogenesis by destruction of HTLV-I infected cells within the central nervous system. Such an hypothesis remains a matter of controversy since some groups have shown that such CTL (both CD8+ or CD4+) are also present in asymptomatic HTLV-I carriers. Recent data have confirmed the high proviral load in PBMC of TSP/ HAM patients (as compared to asymptomatic HTLV-I carriers); however viral expression is very low. There is also recent evidence that more than one copy of HTLV-I proviral DNA may be present in an individual PBMC. One major unanswered question is whether HTLV-I can infect central nervous system cells (neurons, or astrocytes) or if the only HTLV-I infected cells present in the CNS are the infiltrating CD4+ cells. There are published reports supporting both hypotheses. Futhermore, no specific HTLV-I sequences have been related to a given disease outcome, whereas several molecular studies have clearly demonstrated that nucleotide changes in some parts of the HTLV-I genome are correlated with the geographical origin of the patients.

HTLV-I Infections↗
PubMed1996

[Pathologies associated with HTLV-1 virus in Dakar (1992-1995)].

A clinical and laboratory study was conducted in Dakar (Senegal) to assess the involvement of HTLV-1 virus (human T lymphotrophic virus type 1) in various diseases. Patients were enrolled at three locations: the Dermatology Department of the Fann University Hospital Center (845 patients) from 1992 to 1995, the Dermatology Department of the Le Dantec University Hospital Center and the Oncology Department of the Principal Hospital (7 patients) in 1994 and 1995. The incidence of involvement of human retroviruses in neurologic complications seemed low (HTLV-1: 2%, HIV: 3%) and only 6 cases of tropical spastic paraparesis associated with specific anti-HTLV-1 antibodies were diagnosed in 3 men and 3 women with a mean age of 51 years. These cases which were identical to those previously described cases in the West Indies and Japan confirms the existence of this disease in Senegal. In addition 3 cases of isolated facial paralysis were observed in HIV positive patients. Combined HIV/HTLV-1 infection was observed in 3 cases and was not associated with special clinical findings. Adult T-cell leukemia/lymphoma (ATL) was detected in 4 patients including leukemia with proliferation of CD4 and CD25 in two cases and lymphoma in one case. In one case of ATL two proviruses were identified in circulating tumor cells. These are the first cases of ATL to be reported in Senegal. Molecular characterization of part of the envelope gene (gp 21) from patients with PST hospitalized in a neurology ward showed that the virus present in Senegal belonged to the universal HTLV-1 A type. This study indicates that two types of diseases are associated with HTLV-1 infection in Senegal. Further epidemiologic studies will be needed to evaluate the incidence of the virus and of the diseases associated with it. Prevention will depend partly on screening blood donors as has now been started at the Blood Transfusion Center of Dakar.

Adult↗