Revisiting human T-cell lymphotropic virus types 1 and 2 infections among rural population in Gabon, central Africa thirty years after the first analysis.

HTLV-1 infection is considered as highly endemic in central Africa. Thirty years ago, a first epidemiological study was performed in Gabon, central Africa, and revealed that the prevalence varied from 5.0 to 10.5%. To evaluate current distribution of HTLVs in Gabon, 4.381 samples were collected from rural population living in 220 villages distributed within the 9 provinces of country. HTLVs prevalence was determined using two ELISA tests and positive results were confirmed by Western Blot. The overall HTLV-1 seroprevalence was of 7.3% among the rural Gabonese population; with 5.4% for men and 9.0% for women. Prevalence of HTLV-1 differed by province, ranging from 2.3% to 12.5% into the rain forest. Being a woman older than 51 years represented a high risk for HTLV-1 acquisition. Hospitalization, operation/surgery, transfusion and medical abortion or fever, arthritis and abdominal pain are also significant risk factors. In addition, 0.1% of samples were found as HTLV-2 positive, while 12.0% had an indeterminate HTLV serological pattern. HTLV-3 and HTLV-4 were not found. Phylogenetic analysis was performed on 87 samples and demonstrated that HTLV-1 present in Gabon belongs mostly to subtype B, however the rare subtype D was also found. Altogether, our results demonstrate that almost thirty years after the first epidemiological study prevention of HTLVs infection is still an issue in Gabon.

Origin of HTLV-1 in hunters of nonhuman primates in Central Africa.

Of 78 Gabonese individuals who had received bites from nonhuman primates (NHPs) while hunting, 7 were infected with human T lymphotropic virus (HTLV-1). Five had been bitten by gorillas and were infected with subtype B strains; however, a 12-year-old girl who was severely bitten by a Cercopithecus nictitans was infected with a subtype D strain that was closely related to the simian T lymphotropic virus (STLV-1) that infects this monkey species. Her mother was infected with a subtype B strain. These data confirm that hunters in Africa can be infected by HTLV-1 that is closely related to the strains circulating among local NHP game. Our findings strongly suggest that a severe bite represent a risk factor for STLV-1 acquisition.

Acute risk for hepatitis E virus infection among HIV-1-positive pregnant women in central Africa.

BACKGROUND: Hepatitis E virus (HEV), an enterically transmitted pathogen, is highly endemic in several African countries. Pregnant women are at particularly high risk for acute or severe hepatitis E. In Gabon, a central African country, the prevalence of antibodies to HEV among pregnant women is 14.1%. Recent studies have demonstrated unusual patterns of hepatitis E (chronic hepatitis, cirrhosis) among immunodeficient patients. FINDINGS: We investigated the prevalence of antibodies to HEV among pregnant women infected with HIV-1 or HTLV-1 in Gabon. Of 243 samples collected, 183 were positive for HIV-1 and 60 for HTLV-1; 16 women (6.6%) had IgG antibodies to HEV. The seroprevalence was higher among HIV-1-infected women (7.1%) than HTLV-1-infected women (5.0%). Moreover, the HIV-1 viral load was significantly increased (p ≤ 0.02) among women with past-HEV exposure (1.3E+05 vs 5.7E+04 copies per ml), whereas no difference was found in HTLV-1 proviral load (9.0E+01 vs 1.1E+03 copies per ml). CONCLUSIONS: These data provide evidence that HIV-1-infected women are at risk for acute or severe infection if they are exposed to HEV during pregnancy, with an increased viral load.

Recent introduction and rapid dissemination of Chikungunya virus and Dengue virus serotype 2 associated with human and mosquito coinfections in Gabon, central Africa.

BACKGROUND: Chikungunya virus (CHIKV) and Dengue virus serotype 2 (DENV-2) were recently introduced in central Africa, along with Aedes albopictus. Simultaneous outbreaks of CHIKV and DENV-2 have subsequently occurred, in Cameroon in 2006 and Gabon in 2007. METHODS: To study the spread of the 2 viruses, we conducted active surveillance of acute febrile syndromes throughout Gabon between 2007 and 2010. Diagnostic methods included quantitative real-time reverse-transcription polymerase chain reaction, and molecular characterization was based on partial envelope gene sequences. RESULTS: Between 2007 and 2010, 4287 acutely febrile patients were investigated for CHIKV and DENV-2 infections, of whom 1567 were CHIKV-positive, 376 DENV-2-positive, and 37 coinfected. We diagnosed 153 CHIKV and 11 DENV-2 cases in 2008, and 5 CHIKV and 9 DENV-2 cases in 2009. In 2010, CHIKV and DENV-2 caused a second large simultaneous outbreak. Among 2826 acutely febrile patients examined during this outbreak, 1112 were CHIKV-positive, 288 DENV-2-positive, and 28 coinfected. Mosquitoes were collected near the homes of coinfected patients, and 1 Aedes albopictus specimen was found to be positive for both CHIKV and DENV-2. CONCLUSIONS: These findings show the rapid dissemination of CHIKV and DENV-2 within a nonimmune population in a tropical African country, probably facilitated by the spread of Aedes albopictus. This has resulted in major simultaneous outbreaks with numerous coinfections in both human and mosquito.

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

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.

Two distinct variants of simian foamy virus in naturally infected mandrills (Mandrillus sphinx) and cross-species transmission to humans.

BACKGROUND: Each of the pathogenic human retroviruses (HIV-1/2 and HTLV-1) has a nonhuman primate counterpart, and the presence of these retroviruses in humans results from interspecies transmission. The passage of another simian retrovirus, simian foamy virus (SFV), from apes or monkeys to humans has been reported. Mandrillus sphinx, a monkey species living in central Africa, is naturally infected with SFV. We evaluated the natural history of the virus in a free-ranging colony of mandrills and investigated possible transmission of mandrill SFV to humans. RESULTS: We studied 84 semi-free-ranging captive mandrills at the Primate Centre of the Centre International de Recherches Médicales de Franceville (Gabon) and 15 wild mandrills caught in various areas of the country. The presence of SFV was also evaluated in 20 people who worked closely with mandrills and other nonhuman primates. SFV infection was determined by specific serological (Western blot) and molecular (nested PCR of the integrase region in the polymerase gene) assays. Seropositivity for SFV was found in 70/84 (83%) captive and 9/15 (60%) wild-caught mandrills and in 2/20 (10%) humans. The 425-bp SFV integrase fragment was detected in peripheral blood DNA from 53 captive and 8 wild-caught mandrills and in two personnel. Sequence and phylogenetic studies demonstrated the presence of two distinct strains of mandrill SFV, one clade including SFVs from mandrills living in the northern part of Gabon and the second consisting of SFV from animals living in the south. One man who had been bitten 10 years earlier by a mandrill and another bitten 22 years earlier by a macaque were found to be SFV infected, both at the Primate Centre. The second man had a sequence close to SFVmac sequences. Comparative sequence analysis of the virus from the first man and from the mandrill showed nearly identical sequences, indicating genetic stability of SFV over time. CONCLUSION: Our results show a high prevalence of SFV infection in a semi-free-ranging colony of mandrills, with the presence of two different strains. We also showed transmission of SFV from a mandrill and a macaque to humans.

Protective properties of non-nucleoside reverse transcriptase inhibitor (MC1220) incorporated into liposome against intravaginal challenge of Rhesus macaques with RT-SHIV.

In the absence of an effective vaccine against HIV, it is urgent to develop an effective alternative such as a microbicide. Single and repeated applications of MC1220 microbicide were evaluated in macaques. First, animals were given a single application of 0.5% or 1.5% MC1220-containing liposomal gel. A second group were treated with 0.5% MC1220 once a day for 4 days. The control groups were treated by liposomal gel alone. Thirty minutes after the last application, animals were challenged with RT-SHIV. In the first protocol, 2 of 4 animals treated by 0.5% of the MC1220 and 2 of 5 treated by 1.5% were protected. In the second protocol, 3 of 5 treated animals were protected and 5 of 5 controls were infected. The RNA viral load at necropsy was significantly lower (p=0.05) in treated-infected animals than in controls. In both protocols, the number of CD4+ T cells was lower at viremia peak in infected than in protected animals.

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.

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

The transmembrane domains of the prM and E proteins of yellow fever virus are endoplasmic reticulum localization signals.

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 alpha-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.

Role of the transmembrane domains of prM and E proteins in the formation of yellow fever virus envelope.

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.