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A Gessain

Publications and source records attributed to A Gessain.

At least 73 records · Page 4Linked to original sources

Genomic evolution, patterns of global dissemination, and interspecies transmission of human and simian T-cell leukemia/lymphotropic viruses.

Using both env and long terminal repeat (LTR) sequences, with maximal representation of genetic diversity within primate strains, we revise and expand the unique evolutionary history of human and simian T-cell leukemia/lymphotropic viruses (HTLV/STLV). Based on the robust application of three different phylogenetic algorithms of minimum evolution-neighbor joining, maximum parsimony, and maximum likelihood, we address overall levels of genetic diversity, specific rates of mutation within and between different regions of the viral genome, relatedness among viral strains from geographically diverse regions, and estimation of the pattern of divergence of the virus into extant lineages. Despite broad genomic similarities, type I and type II viruses do not share concordant evolutionary histories. HTLV-I/STLV-I are united through distinct phylogeographic patterns, infection of 20 primate species, multiple episodes of interspecies transmission, and exhibition of a range in levels of genetic divergence. In contrast, type II viruses are isolated from only two species (Homo sapiens and Pan paniscus) and are paradoxically endemic to both Amerindian tribes of the New World and human Pygmy villagers in Africa. Furthermore, HTLV-II is spreading rapidly through new host populations of intravenous drug users. Despite such clearly disparate host populations, the resultant HTLV-II/STLV-II phylogeny exhibits little phylogeographic concordance and indicates low levels of transcontinental genetic differentiation. Together, these patterns generate a model of HTLV/STLV emergence marked by an ancient ancestry, differential rates of divergence, and continued global expansion.

Animals↗

Evolutionary inferences of novel simian T lymphotropic virus type 1 from wild-caught chacma (Papio ursinus) and olive baboons (Papio anubis).

A serological survey of 22 wild-caught South African (Transvaal) chacma baboons (Papio ursinus) and eight olive baboons (Papio anubis) from Kenya indicates that 13 P. ursinus and one P. anubis have antibodies reacting with human T cell leukemia/lymphoma virus type 1 (HTLV-1) antigens, whereas three P. ursinus had a indeterminate reactivity on Western blot analysis. With six primer sets specific to either HTLV-1-Simian T-cell leukemia virus type 1 (STLV-1) or HTLV-2 and encompassing long terminal repeat (LTR), gag, pol, env, and tax sequences, polymerase chain reaction was performed on genomic DNA from peripheral blood mononuclear cells of 18 animals, and the presence of HTLV-1-STLV-1-related viruses was determined in 13 seropositive and three seroindeterminate animals but not in the two HTLV seronegative individuals. Proviral DNA sequences from env (522 bp), pol (120 bp), and complete (755 bp) or partial (514 bp) LTR were determined for three STLV-1-infected P. ursinus and one P. anubis. Comparative and phylogenetic analyses revealed that P. anubis (Pan-486) sequence clusters with one (Pan-1621) of two previously described P. anubis STLV-1. Likewise, P. ursinus viruses (Pur-529, Pur-539, and Pur-543) form a distinct group, different from all known HTLV-1 but closely affiliated with two STLV-1 strains from South African vervets (Cercopithecus aethiops pygerythrus). This study, reporting the first STLV-1 sequences from wild-caught P. ursinus and P. anubis, corroborates the hypothesis of cross-species transmissions of STLV-1 in the wild. Further, phylogenetic analyses indicate that the known HTLV-1 strains do not share a common origin with nonhuman primates STLV in South Africa.

Animals↗

Persistent oligoclonal expansion of human T-cell leukemia virus type 1-infected circulating cells in patients with Tropical spastic paraparesis/HTLV-1 associated myelopathy.

The pattern of HTLV-1 replication was assessed through PCR amplification of the 3' proviral integration sites in patients with TSP/HAM at different times. Integration sites were sequenced and oligonucleotides specific for the flanking sequences were synthesized. Together with HTLV-1 LTR specific primers, clonotypic nested PCR was performed on peripheral blood from two patients. The frequencies of five clones studied ranged from 1/300 to 1/1500 PBMCs while four clones persisted for more than 1-5 years. It would seem that Tax driven expansion of T cells may persist for considerable periods of time in TSP/HAM despite strong cellular immunity. This may provide a background for the accumulation of subsequent mutations leading to malignancy.

Adult↗

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.

Adolescent↗

Molecular epidemiology of HTLV-II among United States blood donors and intravenous drug users: an age-cohort effect for HTLV-II RFLP type aO.

Molecular subtyping was used to investigate the epidemiology of human T-lymphotropic virus type II (HTLV-II) in the United States. Nested polymerase chain reaction of the HTLV-II long terminal repeat region followed by restriction fragment length polymorphism (RFLP) analysis was performed on HTLV-II seropositive subjects including 97 U.S. blood donors without major risk factors for HTLV-II infection, 53 injection drug users (IDU), and 10 American Indian blood donors. Three new HTLV-II RFLP types were confirmed with DNA sequencing and phylogenetic analysis. HTLV-II RFLP type aO (Switzer classification) was associated with older age [adjusted odds ratio (OR) 1.06 per year of age, 95% confidence interval (CI) 1.02-1.09] and with Black (OR 5.24, 95% CI 1.90-14.47) and White (OR 4.43, 95% CI 1.67-11.75) race/ethnicity. These data are consistent with an age-cohort effect for HTLV-II RFLP type aO among older White and Black IDU and blood donors. This finding could be explained by an epidemic of non-aO HTLV-II RFLP types among younger persons of Hispanic and other race/ethnicity, superimposed upon endemic HTLV-II RFLP type aO among older Black and White persons.

Adolescent↗

Cutaneous T cell lymphomas: mycosis fungoides, Sezary syndrome and HTLV-I-associated adult T cell leukemia (ATL) in Mali, West Africa: a clinical, pathological and immunovirological study of 14 cases and a review of the African ATL cases.

Cutaneous T cell lymphomas (CTCL) are rare lymphoproliferative diseases, which are frequently suspected to be of viral origin. As very few data were available concerning cutaneous T cell lymphomas in tropical Africa, we undertook a clinical, histopathological, immunological and viro-molecular study of patients with a clinical diagnosis of cutaneous lymphoma, in Bamako, Mali. While prior to this study, no case of CTCL had been reported in this country, 14 patients (five women, nine men; mean age 58 years) with a diagnosis of cutaneous lymphoma were seen over a period of 30 months (1992-1994) in the only dermatological department in Mali. Clinically, the most frequent pattern was an infiltrated erythrodermia similar to Sezary syndrome. Nodular lesions and/or plaques were rarely observed. All these cutaneous tumors were T cell lymphoproliferations, only one expressing the CD8+ antigen. A comprehensive analysis of all the available data permitted characterization of three cases of adult T cell leukemia/lymphoma (ATL) associated with HTLV-I (one definitive case, of leukemic type, with demonstration of clonal integration of HTLV-I proviral genome and two probable ATL cases), three cases of Sezary syndrome (SS), two cases of mycosis fungoides (MF) and five cases of pleomorphic cutaneous lymphoma. In one case, the differentiation between MF and pleomorphic cutaneous lymphoma could not be established. HTLV-I serological and/or molecular markers were restricted to the three ATL cases. From the unique definitive ATL case, a T cell line was established from culture of peripheral blood mononuclear cells and sequence analysis of the env gene and the U3-LTR region demonstrated that the virus present in this patient belonged to the cosmopolitan subtype A. Thus, we report here the first evidence of HTLV-I infection and associated ATL in Mali. This is the second ATL case described for the whole Sahelian region (one ATL of the lymphoma type was reported previously in a Mauritanian patient). Furthermore, we demonstrate that the main types of CTCL described in Europe and North America are also present in this African area and that the prevalence of these diseases is greatly underestimated in such regions. Furthermore, no association was observed between HTLV-I/II infection and SS, MF or pleomorphic cutaneous lymphoma in Mali in contrast to other studies.

Adult↗

Oligoclonal proliferation of human T-cell leukaemia virus type 1 bearing T cells in adult T-cell leukaemia/lymphoma without deletion of the 3' provirus integration sites.

We report a new case of an asymptomatic carrier with a deletion of a 3' HTLV-1 integration site. We further investigated whether these 3' deletions of flanking sequences may explain the oligoclonal pattern of HTLV-1 replication, evidenced by inverse PCR (IPCR) analysis of tumourous samples from patients with adult T-cell leukaemia (ATLL). 48 HTLV-1 3' integration sites, derived from tumourous DNA of five ATLL patients were sequenced. One dominant flanking sequence was obtained in the four samples harbouring a unique band after Southern-blotting. In one sample, which harboured two signals after Southern-blotting, IPCR amplification of diluted tumourous DNA revealed that these two sequences corresponded to one clone harbouring two integrated proviruses rather than to two distinct cellular clones, a result consistent with superinfection of the tumourous sample. In addition to integration sites corresponding to malignant clones, two to six oligoclonal forms were sequenced in four samples. No flanking sequence homology was found between clones derived from each patient, indicating that integration sites deletion in the vicinity of the provirus is a rare event in ATLL. The oligoclonal pattern of HTLV-1 replication in ATLL may result from clonal expansion of non-malignant HTLV-1-bearing clones within the sample and partly from HTLV-1 superinfection of monoclonal tumour cells.

Base Sequence↗

Complete nucleotide sequence of an African human T-lymphotropic virus type II subtype b isolate (HTLV-II-Gab): molecular and phylogenetic analysis.

We report the first complete nucleotide sequence of an African human T-cell lymphotropic virus type II. This new strain, called HTLV-II-Gab (Gab), was obtained from the uncultured peripheral blood mononuclear cells of a 44-year-old healthy Gabonese male who lived in a remote rural area, with neither history of blood transfusion nor sexual intercourse with non-Africans. Using nested PCR, 25 overlapping fragments, representing the entire proviral genome, were obtained, cloned and sequenced. The overall nucleotide sequence comparison with the four other available complete HTLV-II genomes indicated that Gab was more closely related to the HTLV-II subtype b prototypes (98.9, 99.3 and 98.2% nucleotide similarity with G12, NRA and GU respectively) than to the subtype a prototype (95.1% nucleotide similarity with Mo). Restriction profiles studies and phylogenetic analyses confirmed that Gab was a subtype b strain. However, this strain represents a newly described restriction fragment length polymorphism subtype, closely related to one of the rare partially sequenced African isolates originating from a pygmy living in Cameroon (PYGCAM). Nevertheless, the very low genetic divergence observed between this new African strain and the American strains raises several questions on the origins and level of genetic variability over time of this human retrovirus.

Adult↗

Simian T-cell lymphotropic virus type 1 from Mandrillus sphinx as a simian counterpart of human T-cell lymphotropic virus type 1 subtype D.

A recent serological and molecular survey of a semifree-ranging colony of mandrills (Mandrillus sphinx) living in Gabon, central Africa, indicated that 6 of 102 animals, all males, were infected with simian T-cell lymphotropic virus type 1 (STLV-1). These animals naturally live in the same forest area as do human inhabitants (mostly Pygmies) who are infected by the recently described human T-cell lymphotropic virus type 1 (HTLV-1) subtype D. We therefore investigated whether these mandrills were infected with an STLV-1 related to HTLV-1 subtype D. Nucleotide and/or amino acid sequence analyses of complete or partial long terminal repeat (LTR), env, and rex regions showed that HTLV-1 subtype D-specific mutations were found in three of four STLV-1-infected mandrills, while the remaining monkey was infected by a different STLV-1 subtype. Phylogenetic studies conducted on the LTR as well as on the env gp21 region showed that these three new STLV-1 strains from mandrills fall in the same monophyletic clade, supported by high bootstrap values, as do the sequences of HTLV-1 subtype D. These data show, for the first time, the presence of the same subtype of primate T-cell lymphotropic virus type 1 in humans and wild-caught monkeys originating from the same geographical area. This strongly supports the hypothesis that mandrills are the natural reservoir of HTLV-1 subtype D, although the possibility that another monkey species living in the same area could be the original reservoir of both human and mandrill viruses cannot be excluded. Due to the quasi-identity of both human and monkey viruses, interspecies transmission episodes leading to such a clade may have occurred recently.

Amino Acid Sequence↗

[Adult T-cell lymphoma associated with HTLV-1: a familial form].

BACKGROUND: Adult T-cell leukemia-lymphoma (ATL) can occur in siblings infected with HTLV-1. CASE REPORTS: Two Caribbean siblings developed ATL a few years apart. One case has been reported previously. Both individuals had peripheral lymph node T-cell lymphoma and a few atypical lymphocytes on blood smear. Lymphocytosis, bone marrow biopsy, abdominal computed tomographic scanning, and chest radiography were normal. Clonal rearrangement of T-cell receptor was present in skin lesions for both patients and in the blood for one. HTLV-1 serology was positive. Clonal integration of HTLV-1 provirus was demonstrated in skin lesions in one patient and in blood lymphocytes in the other. Chemotherapy, then interferon alpha, were unsuccessful in the first patient. Topical metchloretamine was partially effective for the second patient. DISCUSSION: ATL in siblings is explained by mother-to-child transmission of HTLV-1 infection during breastfeeding.

Adult↗

[Castleman's disease and chromophobe carcinoma of the kidney. An incidental association?].

We report a case of Castleman's disease in a 65-year-old female, revealed by a renal tumor associated with inter-aortico-cava adenopathies and renal chromophobe cell carcinoma. This observation points to the difficulties in differentiating local Castleman's disease, which may be cured by surgical excision, from multicentric disease associated with a dysimmune syndrome of uncertain prognosis. The association of multicentric Castleman's disease with a carcinoma has rarely been described. It could be the emergence of a neoplasia in a context of dysimmunity or Castleman's disease might be related to the production of interleukin 6 by a renal carcinoma.

Adenocarcinoma↗

HTLV-I infection in squirrel monkeys (Saïmiri sciureus) using autologous, homologous, or heterologous HTLV-I-transformed cell lines.

Peripheral blood mononuclear cells (PBMC) from three adult male squirrel monkeys (Saïmiri sciureus) were transformed by human T-cell leukemia/lymphoma virus type I (HTLV-I) by cocultivation with lethally irradiated human MT-2 cells. Three permanent monkey T-cell lines producing HTLV-I were obtained and characterized. Six weeks after inoculation seroconversion was observed in three of three monkeys inoculated with autologous transformed T cells and in two of three monkeys receiving homologous cells. Proviral DNA was detected in their PBMC at various times after inoculation, with the highest proviral load and antibody titers being found in monkeys infected with homologous cells. Monkeys inoculated with heterologous MT-2 cells did not seroconvert, and HTLV-I provirus was detected only transiently in their PBMC. To determine whether in vitro and in vivo HTLV-I infection of squirrel monkey cells led to a selection of monkey-adapted viral mutants, comparative sequencing of the proviral gp21 env between ex vivo monkey HTLV-I-infected PBMC, the inoculum, and MT-2 cells was done and no significant differences were detected. The squirrel monkey, which is naturally free of simian T-cell leukemia/ lymphoma virus, thus appears to be a suitable model for evaluating HTLV-I candidate vaccines and for studying the pathogenesis of HTLV-I.

Animals↗

The tax gene sequences form two divergent monophyletic lineages corresponding to types I and II of simian and human T-cell leukemia/lymphotropic viruses.

Evolutionary associations of human and simian T-cell leukemia/lymphotropic viruses I and II (HTLV-I/II and STLV-I/II) are inferred from phylogenetic analysis of tax gene sequences. Samples studied consisted of a geographically diverse assemblage of viral strains obtained from 10 human subjects and 20 individuals representing 12 species of nonhuman primates. Sequence analyses identified distinct substitutions, which distinguished between viral types I and II, irrespective of host species. Phylogenetic reconstruction of nucleotide sequences strongly supported two major evolutionary groups corresponding to viral types I and II. With the type I lineage, clusters were composed of strains from multiple host species. A genetically diverse, monophyletic lineage consisting of eight new viral strains from several species of Asian macaques was identified. The second lineage consisted of a monophyletic assemblage of HTLV-II/STLV-II strains from Africa and the New World, including an isolate from a pygmy chimp (Pan paniscus) as an early divergence within the lineage. High levels of genetic variation among strains from Asian STLV-I macaque suggest the virus arose in Asia. Evidence of the origin of the type II virus is less clear, but diversity among HTLV-II variants from a single isolated population of Mbati villagers is suggestive but not proof of an African origin.

Amino Acid Sequence↗

Common origin of human T-lymphotropic virus type-I from Iran, Kuwait, Israel, and La Réunion Island.

We found previously that Kuwaiti HTLV-I isolates had two nucleotide substitutions in the most frequently sequenced regions of HTLV-I genome, namely: T-->C 4783 in the pol and T-->C 6569 the env genes. These substitutions were observed rarely in other HTLV-I isolates and seemed to be good markers of the HTLV-I lineage, the "epicentre" of which was located in Mashhad, Iran. To test this hypothesis we sequenced the fragments of HTLV-I genome including sites 4783 and 6569 from seven isolates obtained from the Iranians either living in (five isolates) or originating from (two isolates) Mashhad. RFLP-based tests were also designed and used for typing of the substitutions. All seven isolates were positive for T-->C 4783 and six, from which env fragment was amplifiable, were also positive for T-->C 6569. It is highly probable that all the isolates from Mashhadi Jews belong to the same HTLV-I lineage, although they were not typed yet for the presence of T-->C 6569 substitution. Only 2 "non-Middle Eastern" HTLV-1, both from La Réunion Island were positive for both of the substitutions. Another possible member of Mashhadi lineage of HTLV-I is one isolate from southern India and two isolates from the American Indians, British Columbia, Canada. The determination of the T-->C 4783 and T-->C 6569 markers in HTLV-I isolates of different geographical/ethnic origin may be useful for the reconstruction of the routes of HTLV-I spread from the Middle East and/or Indian subcontinent to other regions of the world and, possibly, for gaining insights into the origin of HTLV-I in Asia.

Adult↗

Human herpes virus 8 (Kaposi's sarcoma herpes virus) and malignant lymphoproliferations in France: a molecular study of 250 cases including two AIDS-associated body cavity based lymphomas.

The new human herpes virus 8 (HHV8) was recently detected in cases of body cavity based lymphoma (BCBL), a rare B cell lymphoma, mostly AIDS-associated. We investigated for HHV8 DNA sequences a series of 250 B or T cell lymphoproliferative malignancies, as seen in France, including 126 leukemias and 124 lymphomas (232 non-AIDS-associated and 18 AIDS-associated tumors). HHV8 sequences were detected in only three patients. The first two were homosexual males, HIV-infected since 1985 who suffered from a BCBL initially characterized in one case by a pleural lymphomatous effusion and a peritoneal one in the other case. A high level of HHV8 copies was detected in the tumoral cells of these two BCBL. In contrast, in the third positive patient who had an AIDS-associated immunoblastic lymphoma, the HHV8 sequences level was quite low. In the two BCBL patients, the HHV8-infected clonal B cells had a large immunoblastic feature with an indeterminate phenotype and were also infected by Epstein-Barr virus. In one BCBL case, a semiquantitative PCR analysis revealed that the HHV8 sequences were much more abundant in the effusion tumor cells than in the cutaneous Kaposi's biopsy while no HHV8 sequence was detectable in the peripheral blood lymphocytes. This study reports HHV8-associated BCBL in European AIDS patients and confirms that HHV8 is present at a high copy number in the tumoral B cells of this malignancy. Furthermore, HHV8 does not seem to play a pathogenic role in any of the other T or B malignant lymphoid neoplasias studied so far. This study also stresses the necessity for quantification studies in interpretation of a positive PCR analysis for HHV8 sequences, especially in patients at risk for HIV infection or Kaposi's sarcoma.

Adult↗

Demographic, ethnic, and geographic differences between human T cell lymphotropic virus (HTLV) type I-seropositive carriers and persons with HTLV-I Gag-indeterminate Western blots in Central Africa.

Using stringent Western blot (WB) criteria, human T cell lymphotropic virus (HTLV) type I seroprevalence among 3783 persons from representative rural populations of Cameroon averaged 1.1% and was higher in females (1.5%) and in Pygmies (2.0%), increasing with age. Furthermore, an HTLV-I Gag-indeterminate WB profile (HGIP), exhibiting strong reactivities to p19, p26, p28, p32, p36, and pr 53 but lacking both p24 and env reactivity, was observed in 1.6% of the same populations. The prevalence of the HGIP was similar between males and females, did not increase with age, and appeared to cluster in tropical forests of southern Cameroon, especially among Pygmies (reaching 4%). These contrasting epidemiologic features, together with the lack of detection by polymerase chain reaction of HTLV-I sequences in the peripheral blood mononuclear cells of the persons with HGIP, strongly suggest that such a WB profile does not appear to reflect an HTLV-I-related viral infection but possibly an environmental (viral or parasitic) factor endemic in tropical rain forest areas.

Adolescent↗