[Genetic diversity and evolution of primate Gammaherpesvirinae]. / Diversité génétique et évolution des Gammaherpesvirinae de primates.

The Gammaherpesvirinae sub-family is divided into two genera, the Lymphocryptovirus and the Rhadinovirus. Until recently, Epstein-Barr virus (EBV), the human prototype of the Lymphocryptovirus genus, and simian homologues have only been detected in humans and Old World non-human primates. In other respects, the Rhadinovirus genus was only represented by Herpesvirus saimiri and Herpesvirus ateles of New World monkey species. Therefore, the general thinking at that time was that the separation of the continents resulted in drastic changes in the Gammaherpesvirinae evolution. The discovery of the human herpesvirus 8 (HHV8), belonging to the Rhadinovirus genus, followed by the identification of CalHV3 (Callitrichine herpesvirus 3) a lymphocryptovirus of marmoset, challenged this old paradigm. The recent description of numerous viruses belonging to the Gammaherpesvirinae subfamily from different Old and NewWorld primate species let to develop and to support co-speciational evolution hypotheses of these viruses and their hosts. This review focuses on our current knowledge of the genetic diversity and evolution of primate Gammaherpesvirinae.

Genetic diversity and phylogenetic analysis of human immunodeficiency virus type 1 subtypes circulating in French Guiana.

We investigated the characterization of different HIV-1 subtypes present in French Guiana by use of three different methods. Serological methods were used for the initial screening, which were then confirmed by the heteroduplex mobility assay (HMA). The V3 env region was subsequently sequenced for phylogenetic analysis, to confirm the subtype of the samples, and to assign a subtype to samples that gave results that were difficult to interpret or discordant by serology or HMA. A total of 221 HIV-1 seropositive samples were typed; 110 of them were confirmed by HMA and 16 were sequenced. Of the 221 samples tested 210 patients (95%) were found to be infected with subtype B, 10 (4.5%) were infected with subtype A, and one patient was infected with subtype F. Phylogenetic analysis demonstrated that the strains from French Guiana were closely related to the subtype A and B subtypes, and that one strain was closely related to an F subtype (100% bootstrap value). Four strains from French Guiana clustered in the subtype A (99% bootstrap value) and the other strains were associated with subtype B (100% bootstrap value). The geographic position of French Guiana suggested that HIV-1 was probably introduced into the country via several routes, and thus the pattern of the HIV-1 epidemic might evolve in the near future.

Health evaluation of translocated free-ranging primates in French Guiana.

Among over 40 mammal species threatened by the filling of a hydroelectric dam reservoir in French Guiana, three species of primates have been translocated, comprising 124 red howler monkeys, six white-faced sakis, and 95 golden-handed tamarins. Health status of the animals was evaluated by direct physical examination and by hematological, biochemical, virological, and parasitological surveys of collected blood. The physical condition of the howlers was slightly worse toward the end of the capture period, but that of sakis and tamarins remained satisfactory. Several ectoparasites (ticks, larvae of dipterous insects, fleas, and lice) were collected, and various wounds, apparently nondebilitating, were recorded in howlers. Hematological and biochemical profiles determined for the three species revealed a slight anemia in howlers. Entamoeba, Strongyloides, and Trypanoxyurus were common in fecal samples of howlers. A survey of blood smears from the three species revealed infection by several types of microfilaria, Trypanosoma rangeli-like and Plasmodium brasilianum in all three, and Trypanosoma cruzi-like in howlers. These infections had no significant impact on the health status or the hematological profiles. Serologic investigations revealed occasional reactions against Toxoplasma gondii, a strong anti-Plasmodium response in the two Cebidae species, and a weaker one in tamarins. Attempts to isolate arbovirus failed, but antibody responses to Mayaro and yellow fever viruses were strong, especially in the howlers. A strong correlation between age and serological status led to a better understanding of the epidemic cycles. Our survey indicates French Guianan primates are reservoirs for several anthropozoonoses, including malaria, Chagas disease, and arboviruses.

High variability of HTLV-I in a remote population of Gabon as compared to that of a similar population of French Guiana.

An anomalous high frequency of ATL was observed in a remote 'noir maroons' village of French Guiana. Since it is not clear if HTLV-I is responsible for different frequencies of disease in different geographical areas, we undertook a comparison of the population with a similar one located in Gabon. We found a much higher degree of gp46 surface envelope glycoprotein sequence conservation in the Guianese village than in the Gabonese one.

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 child's 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.

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.

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. Differences in HAV seroprevalence were found for different age groups, with a large increase in people aged 20-30 years in comparison with those under 20. After logistic analysis, significant differences were found between places of residence; the prevalence of anti-HAV was higher along the Maroni and Oyapock rivers than in the littoral area. The ethnic differences that were observed were generally due to differences in residence. Of all sera, 5.3% were positive for anti-HCV in preliminary tests, but only 1.5% remained positive after confirmation. Brazilians were significantly more frequently infected by HCV than other ethnic groups (4.7%). Sixty-four sera (6.4%) had antibodies to HEV, and differences were found between ethnic groups. Persons of ethnic groups who had emigrated recently to French Guiana had significantly higher seroprevalence rates: 14.6% for Chinese and Hmongs [odds ratio (OR), 4.4; 95% confidence interval (CI), 1.8-10.7], 13.5% for Brazilians (OR, 4.1; CI, 1.8-9.4), and 10.6% for Haitians (OR, 3.1; CI, 1.1-8.7).

Neutralizing activity and antibody reactivity toward immunogenic regions of the human T cell leukemia virus type I surface glycoprotein in sera of infected patients with different clinical states.

The induction of specific neutralizing antibodies is an important part of vaccine strategy against human T cell leukemia virus type I (HTLV-I). A recently developed reporter gene induction assay was used to detect and quantify neutralizing antibodies in sera of HTLV-I-infected patients with different clinical states: Most sera (73/89) displayed an inhibitory activity. Neutralizing antibodies were more frequently detected in sera of patients with tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) or sicca syndrome (SS) (100%) than in sera of patients with adult T cell leukemia (ATL; 50%) or of asymptomatic carriers (AS; 83%). The mean titers in the different groups were significantly different (ATL < AS < TSP/HAM and SS). The antibody reactivity detected by the reporter gene inhibition assay was significantly related to the recognition of the neutralizable immunodominant domain (aa 175-199) of the surface envelope glycoprotein, indicating the importance of this region for potential vaccines.

Immunogenicity of variable regions of the surface envelope glycoprotein of HTLV type I and identification of new major epitopes in the 239-261 region.

The reactivity of sera of 96 individuals infected with human T-cell leukemia virus type I (HTLV-I) was tested against various synthetic peptides corresponding to the gp46 immunodominant antigenic domains: residues 86-107, 175-199, and 239-261. The frequency of reactive sera was higher for 175-199 (93%) than for 239-261 (78%) or 86-107 (24%) with some variations in geographical regions and in diseases. The region 239-261 was extensively analyzed and five (linear or conformational) epitopes were found. The reactivity of sera toward functional or immunodominant domains may depend on the sequence of the infecting virus, and the role of three frequent substitutions (asparagine by tyrosine, proline by serine, and serine by proline or leucine at positions 93, 192, and 250 respectively) was established. Finally, the role of the genetic background of the host may condition the humoral immune response as individuals infected by HTLV-Is harboring the same predicted gp46 peptide sequence may recognize one, several, or all regions examined.