Mélanie Caron

Prevalence and Genetic Diversity of Hepatitis B and Delta Viruses in Pregnant Women in Gabon: Molecular Evidence that Hepatitis Delta Virus Clade 8 Originates from and Is Endemic in Central Africa

ABSTRACT Hepatitis B virus (HBV) surface antigen (HBsAg) was found in 9.2% of 1,186 pregnant women from Gabon, of whom 10.1% had the HBe antigen and 89.9% had anti-HBe antibodies. Antibodies to the hepatitis delta virus (HDV) were found in 15.6% of the HBsAg-positive women. The HBV strains were of the A3 and E genotypes. The HDV strains belonged to HDV clades 1 and 8. These results provide clear evidence that HDV clade 8 is indigenous to Africa.

Cross-species transmission of simian foamy virus to humans in rural Gabon, central Africa

ABSTRACT In order to characterize simian foamy retroviruses (SFVs) in wild-born nonhuman primates (NHPs) in Gabon and to investigate cross-species transmission to humans, we obtained 497 NHP samples, composed of 286 blood and 211 tissue (bush meat) samples. Anti-SFV antibodies were found in 31 of 286 plasma samples (10.5%). The integrase gene sequence was found in 38/497 samples, including both blood and tissue samples, with novel SFVs in several Cercopithecus species. Of the 78 humans, mostly hunters, who had been bitten or scratched by NHPs, 19 were SFV seropositive, with 15 cases confirmed by PCR. All but one were infected with ape SFV. We thus found novel SFV strains in NHPs in Gabon and high cross-species transmission of SFVs from gorilla bites.

Chikungunya, a paradigm of neglected tropical disease that emerged to be a new health global risk.

Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family that causes chronic and incapacitating arthralgia in human populations. Since its discovery in 1952, CHIKV was responsible for sporadic and infrequent outbreaks. However, since 2005, global Chikungunya outbreaks have occurred, inducing some fatalities and associated with severe and chronic morbidity. Chikungunya is thus considered as an important re-emerging public health problem in both tropical and temperate countries, where the distribution of the Aedes mosquito vectors continues to expand. This review highlights the most recent advances in our knowledge and understanding of the epidemiology, biology, treatment and vaccination strategies of CHIKV.

A chikungunya outbreak associated with the vector Aedes albopictus in remote villages of Gabon.

Chikungunya virus (CHIKV) recently caused major urban outbreaks in central African countries such as the Democratic Republic of Congo (DRC), Cameroon, and Gabon. In Gabon, the tiger mosquito Aedes albopictus was shown to be the main CHIKV vector during the 2007 outbreak. This invasive Asian species was first identified in Gabon in early 2007, and was thought to be restricted mainly to coastal provinces where urban epidemic CHIKV foci were recorded. Here we report a CHIKV outbreak in a small cluster of villages isolated in the deep forest of southern Gabon, in which A. albopictus was the main vector. This observation indicates concomitant geographic and ecological spread of CHIKV activity and A. albopictus in remote environments in central Africa, as well as an enhanced risk of propagation of epidemic arboviruses.

Phylogeography, risk factors and genetic history of hepatitis C virus in Gabon, central Africa.

Background The epidemiological and molecular characteristics of hepatitis C virus (HCV) infection in the general population have been poorly investigated in Africa. The aim of this study was to determine the prevalence, genotype distribution and epidemic history of HCV in the Gabonese general population. Methods/Principal Findings A total of 4042 sera collected from adults in 220 villages in all nine administrative areas of the country were screened for antibodies to HCV. HCV NS5B region sequencing was performed for molecular characterization and population genetic analyses. Of 4042 tested sera, 455 (11.2%) were positive. The seroprevalence of HCV varied significantly by administrative area, with the highest rate in Ogooué-Lolo province (20.4%) and the lowest in Ogooué-Maritine province (3.7%). History of parenteral injections, past hospital admission and age over 55 years were independent risk factors for HCV infection (p<0.0001). Phylogenetic analyses showed that 91.9% of the strains were genotype 4 (HCV-4), 5.7% genotype 1 and 2.2% genotype 2. HCV-4 strains were highly heterogeneous, with more than eight subtypes; subtype 4e predominated (57.3%). Coalescence analyses indicated that subtype 4e was the oldest, with an estimated most recent common ancestor of 1702 [95% CI, 1418–1884]. The epidemic profile indicated that it spread exponentially during the first part of the 20th century, probably by iatrogenic transmission. Conclusions/Significance These results confirm the endemicity of HCV subtype 4e in Gabon and show that its spread is due to a cohort effect, with previous, possibly iatrogenic events. More extensive epidemiological studies are needed to better characterize the route of transmission and the dissemination of HCV in Gabon.

Role of the Transmembrane Domains of prM and E Proteins in the Formation of Yellow Fever Virus Envelope

ABSTRACT Flavivirus envelope proteins have been shown to play a major role in virus assembly. These proteins are anchored into cellular and viral membranes by their C-terminal domain. These domains are composed of two hydrophobic stretches separated by a short hydrophilic segment containing at least one charged residue. We investigated the role of the transmembrane domains of prM and E in the envelope formation of the flavivirus yellow fever virus (YFV). Alanine scanning insertion mutagenesis has been used to examine the role of the transmembrane domains of prM and E in YFV subviral particle formation. Most of the insertions had a dramatic effect on the release of YFV subviral particles. Some of these mutations were introduced into the viral genome. The ability of these mutant viruses to produce infectious particles was severely reduced. The alanine insertions did not affect prM-E heterodimerization. In addition, replacement of the charged residues present in the middle of the transmembrane domains had no effect on subviral particle release. Taken together, these data indicate that the transmembrane domains of prM and E play a crucial role in the biogenesis of YFV envelope. In addition, these data indicate some differences between the transmembrane domains of the hepaciviruses and the flaviviruses.

Hepatitis E virus is highly prevalent among pregnant women in Gabon, central Africa, with different patterns between rural and urban areas

Hepatitis E virus (HEV) is highly endemic in several African countries with high mortality rate among pregnant women. Nothing is known about the circulation of this virus in central Africa. We evaluated therefore the prevalence of anti-HEV IgG in samples collected from pregnant women living in the five main cities of Gabon, central Africa. We found that 14.1% (119/840) of pregnant women had anti-HEV IgG. The prevalence differed between regions and between age groups. In 391 newly collected samples from the region where the highest prevalence was found, a significant difference (p < 0.05) in seroprevalence was found between rural (6.4%) and urban (13.5%) areas. These data provide evidence of a high prevalence of HEV in Gabon, providing indirect evidence of past contact with this virus.

Clinical forms of chikungunya in Gabon, 2010.

Background Chikungunya virus (CHIKV) has caused multiple outbreaks in tropical and temperate areas worldwide, but the clinical and biological features of this disease are poorly described, particularly in Africa. We report a prospective study of clinical and biological features during an outbreak that occurred in Franceville, Gabon in 2010. Methodology/Principal Findings We collected, in suspect cases (individuals presenting with at least one of the following symptoms or signs: fever, arthralgias, myalgias, headaches, rash, fatigue, nausea, vomiting, diarrhea, bleeding, or jaundice), blood samples, demographic and clinical characteristics and outcome. Hematological and biochemical tests, blood smears for malaria parasites and quantitative PCR for CHIKV then dengue virus were performed. CHIKV+ patients with concomitant malaria and/or dengue were excluded from the study. From May to July 2010, data on 270 laboratory-confirmed CHIK patients were recorded. Fever and arthralgias were reported by respectively 85% and 90% of patients, while myalgias, rash and hemorrhage were noted in 73%, 42% and 2% of patients. The patients were grouped into 4 clinical categories depending on the existence of fever and/or joint pain. On this basis, mixed forms accounted for 78.5% of cases, arthralgic forms 12.6%, febrile forms 6.7% and unusual forms (without fever and arthralgias) 2.2%. No cases of organ failure or death were reported. Elevated liver enzyme and creatinine levels, anemia and lymphocytopenia were the predominant biological abnormalities, and lymphocytopenia was more severe in patients with high viral loads (p = 0.01). Conclusions/Significance During CHIK epidemics, some patients may not have classical symptoms. The existence of unusual forms and the absence of severe forms of CHIK call for surveillance to detect any change in pathogenicity.

New Insights into Prevalence, Genetic Diversity, and Proviral Load of Human T-Cell Leukemia Virus Types 1 and 2 in Pregnant Women in Gabon in Equatorial Central Africa

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) is highly endemic in areas of central Africa; mother-to-child transmission and sexual transmission are considered to be the predominant routes. To determine the prevalence and subtypes of HTLV-1/2 in pregnant women in Gabon, we conducted an epidemiological survey in the five main cities of the country. In 907 samples, the HTLV-1 seroprevalence was 2.1%, which is lower than that previously reported. Only one case of HTLV-2 infection was found. The HTLV-1 seroprevalence increased with age and differed between regions (P ≤ 0.05), with the highest prevalence (5%) in the southeastern region. A wide range of HTLV-1 proviral loads was observed among the infected women. The level of the proviral load was correlated with a high HTLV-1 antibody titer (P ≤ 0.02). Sequencing of HTLV-1 env and long terminal repeat fragments showed that all but one strain belonged to the central African subtype B; the outlier was of cosmopolitan subtype A. The new strains of subtype B exhibited wide genetic diversity, but there was no evidence of clustering of specific genomes within geographical regions of the country. Some strains were closely related to simian T-cell leukemia virus type 1 strains of great apes, suggesting that in these areas some HTLV-1 strains could arise from relatively recent interspecies transmission. The sole HTLV-2 strain belonged to subtype B. In this study we showed that the prevalence of HTLV-1 in the southeast is one of the highest in the world for pregnant women.

The Transmembrane Domains of the prM and E Proteins of Yellow Fever Virus Are Endoplasmic Reticulum Localization Signals

ABSTRACT The immature flavivirus particle contains two envelope proteins, prM and E, that are associated as a heterodimer. Virion morphogenesis of the flaviviruses occurs in association with endoplasmic reticulum (ER) membranes, suggesting that there should be accumulation of the virion components in this compartment. This also implies that ER localization signals must be present in the flavivirus envelope proteins. In this work, we looked for potential subcellular localization signals in the yellow fever virus envelope proteins. Confocal immunofluorescence analysis of the subcellular localization of the E protein in yellow fever virus-infected cells indicated that this protein accumulates in the ER. Similar results were obtained with cells expressing only prM and E. Chimeric proteins containing the ectodomain of CD4 or CD8 fused to the transmembrane domains of prM or E were constructed, and their subcellular localization was studied by confocal immunofluorescence and by analyzing the maturation of their associated glycans. Although a small fraction was detected in the ER-to-Golgi intermediate and Golgi compartments, these chimeric proteins were located mainly in the ER. The C termini of prM and E form two antiparallel transmembrane α-helices. Interestingly, the first transmembrane passage contains enough information for ER localization. Taken altogether, these data indicate that, besides their role as membrane anchors, the transmembrane domains of yellow fever virus envelope proteins are ER retention signals. In addition, our data show that the mechanisms of ER retention of the flavivirus and hepacivirus envelope proteins are different.