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A Gessain

Publications and source records attributed to A Gessain.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Preliminary study of human Herpesvirus type 8 infection in pregnant women in Dakar (Senegal)].

HHV8 was discovered in 1994 and few studies on this virus have been conducted in Africa. The virus is related to Kaposi sarcoma, an opportunistic affection occurring during HIV infection. No studies have been carried out on this subject in Senegal, a country known for its low KS prevalence even among people living with HIV/AIDS. Thus it will be interesting to explore this field. The aim of our study has been first, to demonstrate the presence of HHV8; second, to evaluate sero-prevalence of the infection in Senegal and third, to determine the specificities of HHV8 infection in our country. We performed our study on 407 pregnant women whose average age was 29.24 years, the majority of whom were Senegalese. HIV serology was done by dot blot for the screening and western blot for the confirmation. For the diagnosis of HHV8 infection, we used the indirect immunofluorescence kit of ABI. HIV infection was low among this study population; 0.5% and no HIV1 infection was mentioned. Among the 407 women, 58 or 14.3% were HHV8 positive and there was no HHV8/HIVco-infection. Regarding marital status, no significant difference was found between HHV8 positive and HHV8 negative among unmarried, monogamous or polygamous women. However, women having had 4 to 5 children were more likely to test positive for HHV8. The difference is significant and a relationship has been established with a p value of 0.02. Regarding pregnancy, HHV8 infection is more closely related to abortion: 17.2% of women who had aborted were HHV8 positive versus 4.9% seronegative. The odds ratio calculation shows a strong correlation with a p value of 0.01. No correlation was found between HHV8 infection of the mother and neonate mortality or Apgar score. However, a relationship did show up between HHV8 infection of the mother and low birth weight. 29.2% of seropositive women had had a child with a birth weight under 2600 g whereas only 16.3% of seronegative women had had babies with low birth weight. We determined that HHV8 is indeed present in Senegal. Further studies should focus on transmission routes as well as the molecular epidemiology of this virus and diseases related to HHV8 infection in Senegal.

Abortion, Spontaneous↗
PubMed2000

[A virus called HTLV-1. Virological and molecular aspects].

A VIRAL PATHOGEN: HTLV-1, the first oncogenic retrovirus discovered in man carries, in addition to the genes coding for its structural protein, genes for capside and matrix (gag), reverse transcriptase and integrase (pol), protease and envelope (env), a unique region (termed pX) of about 2 kb situated at the position 3' of the env gene that encodes for Tax and Rex regulator proteins. TAX AND REX: These two proteins play a role in the viral cycle. Rex acts at the post-transcriptional level; Its capacity to modulate Tax expression could allow the virus to establish a chronic infection with little expression. Tax stimulates viral transcription and also plays a fundamental role in leukecernogenesis by modifying the expression of several genes crucial for cell survival and proliferation. GENETIC STABILITY: The HTLV-1 genome sequence appears to be very stable. Specifically leukernogeneic or neurotrophic strains are unlikely to exist. However, despite this genetic stability, there are molecular variants related to the geographical origin of the virus.

DNA, Viral↗
PubMed2000

[A virus called HTLV-1. Epidemiological aspects].

GEOGRAPHIC DISTRIBUTION AND TRANSMISSION: HTLV-1 is not an ubiquitous virus. 15 to 25 million subjects are estimated to be infected. Endemic areas are recognized in southern Japan, tropical Africa, the Caribbean, some areas in Central and South America, and in few regions of the Middle East and Melanesia. In these endemic zones, 0.5 to 50% of the population, depending on age and gender, have specific antibodies against HTLV-1 antigens. Interhuman transmission can occur from mother to child by prolonged breast feeding, from men to women by sexual intercourse, and from blood exposure via infected lymphoid cells. MOLECULAR EPIDEMIOLOGY: Molecular epidemiology studies have evidenced several molecular types or genotypes of HTLV-1 linked to the geographical origin of the infected population rather than to the associated pathology (leukemia versus neuromyelopathy). The high stability of the HTLV-1 genome is probably related to clonal expansion of infected cells conjugated to the minimal use of the reverse transcriptase. This low variability has been used as a molecular tool to better understand the origin, the evolution and the dissemination of this retrovirus. The current distribution of HTLV-1, and its simian homologue STLV-1, results from at least 4 events: transmission of STLV-1 between different monkey species, transmission of STLV-1 to humans, persistence of HTLV-1 in isolated human populations, and finally global and more recent distribution of HTLV-1 (mainly the cosmopolite subtype) subsequent to migration of virus-infected populations.

Animals↗
PubMed2000

Molecular characterization and phylogenetic analyses of a new simian T cell lymphotropic virus type 1 in a wild-caught african baboon (Papio anubis) with an indeterminate STLV type 2-like serology.

STLV-1 viruses are closely related to HTLV-1 and infect many African monkey species. Seroreactivities of monkeys infected by STLV-1 are nearly identical to those of HTLV-1-infected individuals. In some cases, STLV-1 are, sequence-wise, indistinguishable from HTLV-1, and cannot be separated from them on the basis of phylogenetic analyses. HTLV-2-related simian viruses have been rarely reported. Such STLV-2 viruses, present in African bonobo (Pan paniscus), possess a genomic organization related to but different from all known HTLV-2 subtypes. We report here the molecular characterization and the subtyping of a new STLV-1 in a wild-caught baboon (Papio anubis) whose serum exhibited an indeterminate STLV-2-like serology (p24, GD21, MTA-1 with no p19). In the env and LTR regions, this virus is phylogenetically related to the large African STLV-1 group, but does not cluster with any STLV-1 baboon sequence. The complete p19 sequence reveals amino acid changes at critical positions. This is the first report of an African STLV-1 virus leading to an STLV-2-like serological profile in its host.

Amino Acid Sequence↗
PubMed2000

Molecular epidemiology of human herpesvirus 8 in africa: both B and A5 K1 genotypes, as well as the M and P genotypes of K14.1/K15 loci, are frequent and widespread.

We have studied 52 new HHV8 strains by sequencing the complete hypervariable K1 gene and genotyping the K14.1/K15 loci located at both sides, respectively, of the viral genome. The samples originated from 49 patients with Kaposi's sarcoma (KS; 32 patients), multicentric Castleman's disease (MCD; 12 patients), or primary effusion lymphoma (PEL; 5 patients). Among these patients, 32 were of African origin (West and Central African countries and Creoles from French Guiana) and the 17 others were mostly French homosexuals. Comprehensive phylogenetic studies allowed the identification of distinct groups within the three already known main subtypes. Interestingly, two new sequences that did not cluster within a known subtype or group could be considered as prototypes of early/ancient variants of the C subtype and A/C set, respectively. Among the 32 African strains, the majority were either of the B subtype (13 cases) or of the A5 group (11 cases), indicating that this latter genotype is frequent and widespread in Africa. In contrast, a subtype C strain infected most of the 17 other patients. PCR-based genotyping of the K14.1/K15 loci revealed an overall predominance of P subtype, except in the A5 and B K1 groups, in which the P and M alleles were equally represented. The implications of these data on the evolution and spread of HHV8 among human African populations are discussed.

Adult↗
PubMed2000

Durable remission after aggressive chemotherapy for very late post-kidney transplant lymphoproliferation: A report of 16 cases observed in a single center.

PURPOSE: Posttransplant lymphoproliferative diseases (PTLDs) represent a group of potentially lethal lymphoid proliferations that may complicate the course of solid organ transplantation. Although early-onset PTLDs frequently have a favorable outcome, late-onset PTLDs behave more alike aggressive lymphoma. We report a monocentric retrospective study that focused on PTLDs occurring later than 1 year after kidney transplantation (very late-onset PTLDs) to define their incidence, clinical presentation, pathologic features, and outcome. We particularly emphasized the follow-up of patients treated with conventional chemotherapy. PATIENTS AND METHODS: The medical histories of all patients who developed very late-onset PTLD in our institution were reviewed, and diagnostic biopsy materials were retrospectively studied. RESULTS: Very late-onset PTLDs were diagnosed in 16 (1.1%) of 1,421 patients. Mean (+/- SD) time to tumor onset was 103.93 +/- 70.88 months. Most tumors were Epstein-Barr virus-related monomorphic large-cell PTLDs of B phenotype. Ten patients received conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone regimen). Two of them died within 2 months, two achieved partial remission, and six achieved definitive complete remission. Overall median survival time was 13 months and rose to 27 months in the treated group. The main cause of mortality was sepsis. None of the treated patients experienced rejection despite withdrawal of immunosuppressive treatment. CONCLUSION: Despite characteristics of aggressive lymphoma, very late-onset PTLDs after renal transplantation may respond to conventional chemotherapy. However, because a high rate of infectious complications occurred, new therapeutic strategies, such as combinations of anti-CD20 monoclonal antibodies and lower doses of chemotherapy, are warranted.

Adult↗
PubMed2000

High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis.

Adult T cell leukemia (ATLL) develops in 3 - 5% of HTLV-1 carriers after a long period of latency during which a persistent polyclonal expansion of HTLV-1 infected lymphocytes is observed in all individuals. This incubation period is significantly shortened in HTLV-1 carrier with Strongyloides stercoralis (Ss) infection, suggesting that Ss could be a cofactor of ATLL. As an increased T cell proliferation at the asymptomatic stage of HTLV-1 infection could increase the risk of malignant transformation, the effect of Ss infection on infected T lymphocytes was assessed in vivo in HTLV-1 asymptomatic carriers. After real-time quantitative PCR, the mean circulating HTLV-1 proviral load was more than five times higher in HTLV-1 carriers with strongyloidiasis than in HTLV-1+ individuals without Ss infection (P<0.009). This increased proviral load was found to result from the extensive proliferation of a restricted number of infected clones, i.e. from oligoclonal expansion, as evidenced by the semiquantitative amplification of HTLV-1 flanking sequences. The positive effect of Ss on clonal expansion was reversible under effective treatment of strongyloidiasis in one patient with parasitological cure whereas no significant modification of the HTLV-1 replication pattern was observed in an additional case with strongyloidiasis treatment failure. Therefore, Ss stimulates the oligoclonal proliferation of HTLV-1 infected cells in HTLV-1 asymptomatic carriers in vivo. This is thought to account for the shortened period of latency observed in ATLL patients with strongyloidiasis. Oncogene (2000) 19, 4954 - 4960

Adult↗
PubMed2000

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.

Adolescent↗
PubMed2000

Common human T cell leukemia virus type 1 (HTLV-1) integration sites in cerebrospinal fluid and blood lymphocytes of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis indicate that HTLV-1 crosses the blood-brain barrier via clonal HTLV-1-infected cells.

In the spinal cord of patients with human T cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), infiltrating CD4(+) lymphocytes seem to be the major reservoir for the virus. Little, however, is known about the mechanisms by which HTLV-1 crosses the blood-brain barrier. An oligoclonal proliferation of HTLV-1-infected CD4 lymphoid T cells is present in the peripheral blood of all HTLV-1-infected individuals. Here, such oligoclonal distribution of HTLV-1-infected cells is evidenced in the cerebrospinal fluid (CSF) derived from 5 patients with HAM/TSP. Furthermore, clonal populations of HTLV-1-infected lymphocytes sharing the same HTLV-1 proviral flanking sequences (i.e. , integration sites in the cellular DNA), and thus derived from a single HTLV-1-infected progenitor, were found, for a given patient, in both the CSF and the peripheral blood. These data demonstrate that HTLV-1 crosses the blood-brain barrier by migration of HTLV-1-infected lymphocytes in vivo.

Adult↗
PubMed2000

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.

Adult↗
PubMed2000

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.

Adolescent↗
PubMed2000

Deletion of the p16INK4A gene in ex vivo acute adult T cell lymphoma/leukemia cells and methylation of the p16INK4A promoter in HTLV type I-infected T cell lines.

The stoichiometry of the p16INK4A and p15INK4B proteins bound to the cyclin D-CDK4/6 complex regulates the entry of cells into the G1 phase of the cell cycle. Thus, their level of expression is essential in maintaining regulated cell growth. In several tumors, deletion of these genes has been reported and, more recently, promoter methylation has been suggested as an alternative mechanism to decrease the expression of these cell cycle inhibitor proteins. Here, we studied the methylation status and the integrity of the p16INK4A and p15INK4B genes in 8 chronically HTLV-I-infected T cell lines and in ex vivo cells from 14 ATLL patients. Deletion of the locus carrying both genes was not found in the HTLV-I-infected T cell lines but was found in seven of eight acute ATLL cases and in none of the PBMCs from the chronic cases or the affected lymph nodes of the lymphoma type. In contrast, partial or complete methylation of one or both genes was found only in chronically HTLV-I T cells. Thus, HTLV-I infection targets the p16INK4A and p15INK4B loci both in vitro and in vivo, although the mechanisms may differ.

Cell Line, Transformed↗
PubMed2000

Monoclonality or oligoclonality of human herpesvirus 8 terminal repeat sequences in Kaposi's sarcoma and other diseases.

BACKGROUND: Infection with human herpesvirus 8 (HHV8), also termed Kaposi's sarcoma (KS)-associated herpesvirus, is associated with all forms of KS, with primary effusion lymphoma (PEL), and with some forms of multicentric Castleman's disease (MCD), but the pathogenic role of HHV8 in these tumors and the clonal nature of KS are still unclear. The purpose of this study was to examine whether the number of terminal repeats (TRs) contained in the fused TR region of HHV8 could be used as a marker of clonality in HHV8-associated tumors. METHODS: Pulsed-field gel electrophoresis (PFGE) and multiple-probe Southern blot analysis of the HHV8 TR region were performed on high-molecular-weight DNA obtained from tumoral KS, PEL, and MCD lesions. RESULTS: These analysis showed that the fused TR region contains a large but variable number of TR units (ranging from 16 to 75) and that the viral genome is present as extrachromosomal circular DNA in these tumors in vivo, with occasional ladders of heterogeneous linear termini reflecting lytic replication. All PEL tumors and PEL-derived cell lines as well as some KS tumors contained monoclonal or oligoclonal fused TR fragments; however, the TR region appeared polyclonal in MCD tumors and in a few KS lesions. CONCLUSION: Several KS and PEL lesions are monoclonal expansions of a single infected cell, suggesting that HHV8 infection precedes tumor growth and thus supporting an etiologic role of latent HHV8 in these proliferations. Our finding that nodular KS lesions display all possible patterns of clonality supports the model according to which KS begins as a polyclonal disease with subsequent evolution to a monoclonal process.

Adult↗
PubMed2000

Evidence for the chronic in vivo production of human T cell leukemia virus type I Rof and Tof proteins from cytotoxic T lymphocytes directed against viral peptides.

Human T cell leukemia virus type I (HTLV-I) is a persistent virus that causes adult T cell leukemia and tropical spastic paraparesis/HTLV-I-associated myelopathy. Studies on rabbits have shown that viral proteins encoded by the open reading frames pX-I and pX-II are required for the establishment of the persistent infection. To examine the in vivo production of these proteins in humans, we have investigated whether cytotoxic T lymphocytes isolated from HTLV-I-infected individuals recognized pX-I and pX-II peptides. CD8(+) T lymphocytes to pX-I and pX-II peptides were detected in HTLV-I-infected individuals, whatever their clinical status, and even in the absence of any antigenic restimulation. These findings indicate that the HTLV-I pX-I and pX-II proteins are chronically synthesized in vivo, and are targets of the natural immune response to the virus.

Amino Acid Sequence↗
PubMed2000

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.

AIDS-Related Opportunistic Infections↗
PubMed2000

Evidence against a direct cytotoxic effect of alpha interferon and zidovudine in HTLV-I associated adult T cell leukemia/lymphoma.

The combination of the anti-viral agents, zidovudine (AZT) and interferon-alpha (IFN), is a potent treatment of HTLV-I-associated adult T cell leukemia/lymphoma (ATL). In this study we investigate the possible mechanism of action of this combination by examining several cellular parameters including cell proliferation, cell cycle distribution and apoptosis. The ATL-derived T cell lines HuT-102 and MT-2 served as models. HTLV-I negative T cell lines (CEM and Jurkat) were used as controls. No significant modification of cell growth was observed except at suprapharmacological doses of AZT and IFN. Moreover, these effects were less pronounced in HTLV-I-infected cell lines compared to control cell lines. AZT and IFN treatment did not induce any significant modification of the expression of bcl-2 and p53. Interestingly no in vitro cytotoxic effect of AZT/IFN combination was observed on fresh leukemic cells derived from an acute ATL patient at diagnosis despite achievement of in vivo complete remission using the same therapy. These results suggest that the therapeutic effect of AZT and IFN is not through a direct cytotoxic effect of these drugs on the leukemic cells.

Aged↗