Jean-François Pouliquen

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 childs 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. Int. J. Cancer 82:832–836, 1999.

Increased expression of telomere length regulating factors TRF1, TRF2 and TIN2 in patients with adult T-cell leukemia.

Here, we report that freshly isolated unstimulated adult T‐cell leukemia (ATL) cells present high telomerase activity compared to asymptomatic carriers or normal donors. In spite of this high telomerase activity, ATL cells retained shorter telomeres compared to those of uninfected cells isolated from the same patients. Because the safeguarding of telomere length is critical to the unlimited proliferation of tumor cells, we investigated the underlying mechanism for short telomere maintenance in ATL cells. Transcriptional and posttranscriptional expression of telomere‐binding proteins TRF1, TRF2, TIN2 and POT1, known to regulate telomere homeostasis and protection, were evaluated. We found that TRF1 and TRF2 are overexpressed in in vivo patients samples from ATL but not asymptomatic carriers, while levels of POT1 expression did not specifically increase in ATL. To gain insights into the regulation of TRF genes in HTLV‐I infected cells, we investigated the expression of TIN2, a regulator of these genes, and found an increase in TIN2 expression in ATL patients. Together our results underscore the importance of telomerase and telomere length regulating factors as novel markers for ATL disease progression and as potential therapeutic targets for the treatment of HTLV‐I‐associated malignancies.

Demographic and familial characteristics of HTLV-I 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 11 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. Int. J. Cancer 76:331–336, 1998.© 1998 Wiley‐Liss, Inc.

Serological and Molecular Evidence That Human Herpesvirus 8 Is Endemic among Amerindians in French Guiana

We evaluated the presence of human herpesvirus 8 (HHV-8) infection among groups of Amerindians in French Guiana. The overall prevalence of antibodies against lytic HHV-8 antigens was 23.0% (180/781), increasing from 18.4% in children <6 years old to approximately 30% in older persons (>45 years). Seroprevalence was higher in Amerindians living in remote localities than it was in those living in the coastal region. Analysis of a 725-base pair fragment of the K1 gene amplified from DNA from a Wayampi Amerindian showed that the virus belonged to molecular subtype E, which has hitherto been found in only a few Amerindians in Brazil and Ecuador.

A sero-epidemiological study of malaria in human and monkey populations in French Guiana

This paper describes a sero-epidemiological study of malaria prevalence in French Guiana. An immunofluorescence assay and an enzyme-linked immunosorbent assay were used to detect antibodies against blood-stage antigens and synthetic peptides mimicking the repetitive epitope of the sporozoites of Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae/brasilianum, in 218 human sera and 113 non-human primate sera collected in French Guiana. Almost all the monkey sera tested had antibodies against malaria blood-stages (98%) and a large majority (73%) also tested positive with the P. malariae/brasilianum circumsporozoite peptide. A number of primate samples also reacted positively with P. falciparum NANP repeats in a very specific manner, suggesting that monkeys in the rainforest are bitten by mosquitoes infected with human malaria parasites. Seroprevalences were lower in the humans tested but Indian tribes on the borders with Suriname and Brazil were clearly more exposed to malaria than other ethnic groups, with a prevalence of nearly 70% seropositivity. P. vivax infections accounted for much of the observed pattern of reactivity, but there was also a high frequency of positive reactions to the P. brasilianum/malariae peptide. Similarly, a large proportion of the sera obtained from Bush Negro populations tested positive for P. malariae/brasilianum repeats. These data add to the emerging evidence that non-human primates might constitute a natural reservoir, not only for simian, but also for human malaria, and therefore suggest that they might be responsible for the maintenance of foci of P. malariae, and possibly of other malaria species, in isolated areas of the Amazonian rainforest.

High Seroprevalence of Human T-Cell Lymphotropic Virus Type 1 in Blood Donors in Guyana and Molecular and Phylogenetic Analysis of New Strains in the Guyana Shelf (Guyana, Suriname, and French Guiana)

ABSTRACT The prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 in blood donors in Guyana has never been estimated. We evaluated the prevalence of these viruses in blood donors by enzyme-linked immunosorbent assay and Western blotting and showed a prevalence of HTLV-1 of 1.3%; no HTLV-2 was detected. Female donors had a much higher HTLV-1 seroprevalence (3.6%) than male donors (0.7%). HTLV-1-seropositive donors tended to be slightly older than the average age for the total pool of donors. We also investigated the phylogenetic and molecular characteristics of HTLV-1 strains in Guyana and compared them with those identified in Suriname and French Guiana. Analysis of portions of the env and long terminal repeat nucleotide sequences showed that all the strains in Guyana and Suriname, like those in French Guiana, belonged to the transcontinental group of cosmopolitan subtype A. The similarities were greater between strains from Suriname and Guyana than between strains from Suriname and Guyana and those from French Guiana. Nevertheless, our results confirm that the HTLV-1 strains in all three countries have a common African origin.

Genetic diversity and molecular evolution of human and non-human primate Gammaherpesvirinae.

The Gammaherpesvirinae sub-family is divided into two genera: Lymphocryptovirus and Rhadinovirus. Until the middle of the 1990s, the Rhadinovirus genus was only represented by Herpesvirus saimiri and Herpesvirus ateles, which infect New World monkey species. Until the year 2000, Epstein-Barr virus (EBV), the human prototype of the Lymphocryptovirus, and simian homologues had only been detected in humans and Old World non-human primates. It was thought, therefore, that the separation of the continents had resulted in drastic changes in Gammaherpesvirinae evolution. The discovery of Kaposis sarcoma-associated herpesvirus in humans, belonging to the Rhadinovirus, followed by the identification of CalHV3 (Callitrichine herpesvirus 3), a lymphocryptovirus of the marmoset, challenged this paradigm. The description of numerous viruses belonging to this sub-family from various Old and New World primate species enabled a cospeciation hypothesis for these viruses and their hosts to be developed. This review focuses on the current knowledge of primate Gammaherpesvirinae genetic diversity and molecular evolution. We discuss the various theories based on current genetic data regarding evolutionary relationships between lymphocryptoviruses of Old World primates, the use of these data as a tool to study evolutionary relationships between New World monkey species, and the possible existence of a ninth human herpesvirus belonging to the Rhadinovirus genus.

Novel Gamma-1 Herpesviruses Identified in Free-Ranging New World Monkeys (Golden-Handed Tamarin [Saguinus midas], Squirrel Monkey [Saimiri sciureus], and White-Faced Saki [Pithecia pithecia]) in French Guiana

ABSTRACT The recent finding of a novel Epstein-Barr virus-related lymphocryptovirus (CalHV-3) in a captive colony of common marmoset (Callithrix jacchus) in the United States modifies the view that the host range of lymphocryptovirus is restricted to humans and Old World primates. We investigated the presence of Epstein-Barr virus-related viruses in 79 samples of New World monkeys caught in the wild, including six species of the Cebidae family and one of the Callitrichidae, living in the rain forest of French Guiana. Using a degenerate consensus PCR method for the herpesvirus DNA polymerase gene, we identified three novel lymphocryptoviruses from golden-handed tamarin (Saguinus midas) of the Callitrichidae family and squirrel monkey (Saimiri sciureus) and white-faced saki (Pithecia pithecia) of the Cebidae family. With the CalHV-3 strain, these three novel viruses constitute a well-supported phylogenetic clade in the Lymphocryptovirus genus, which is clearly distinct from the lineage of Old World lymphocryptovirus, hosted by catarrhine monkeys and humans. In tamarins, the prevalence of the novel lymphocryptovirus was more than 50%, indicating that it circulates well in the wild population, perhaps due to specific ecoethological patterns such as confrontations and intergroup migration. The detection and partial molecular characterization of the polymerase gene of three novel Gamma-1-Herpesvirinae from New World monkeys caught in the wild clearly indicate that free-ranging populations of platyrrhine are natural hosts of lymphocryptoviruses. Further characterization of these novel viruses will provide new insight not only into the origin and evolution of Gammaherpesvirinae but also into their pathogenicity.

Adult T-cell leukaemia/lymphoma-like human T-cell leukaemia virus-1 replication in infective dermatitis.

Summary. Adult T‐cell leukaemia/lymphoma (ATLL) is a malignant T‐cell proliferation that occurs in 3–5% of individuals infected with human T‐cell leukaemia virus‐1 (HTLV‐1). HTLV‐1 infection is also linked to the development of infective dermatitis (ID), an exudative dermatitis of children that has been proposed as a cofactor of ATLL. Here, HTLV‐1 replication was investigated over time in a girl with ID and multiparasitic infestation including strongyloidiasis, a disease also known to predispose HTLV‐1 carriers to ATLL. Quantitative polymerase chain reaction (PCR) revealed extremely high proviral loads. During the 2‐year period of the present study, the proportion of circulating infected cells ranged between 12% and 36%. Quadruplicate linker‐mediated PCR amplification of HTLV‐1 flanking sequences identified a pattern of extensive and persistent oligoclonal expansion of infected lymphocytes. As viral loads, both the number and the degree of infected T‐cell expansion were independent of treatment or clinical signs. However, the temporal fluctuation of proviral loads correlated significantly with the degree of infected T‐cell expansion, but not with the overall number of detected clones. This pattern of HTLV‐1 replication over time is very different from that observed in asymptomatic carriers and reminiscent of that observed in ATLL, a result consistent with the proposal of ID as an ATLL cofactor.

Prevalence of antibodies to hepatitis A, C, and E viruses in different ethnic groups in French Guiana

In order to determine the prevalence of antibodies to hepatitis A, C, and E viruses (HAV, HCV, and HEV) in the various ethnic groups and areas of French Guiana, sera (996 for HCV and HEV, 941 for HAV) were tested for antibodies to these viruses using ELISAs.