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This study provides insight into the genetic diversity of HDV and a clear view of its geographical localization and allows speculation as to the worldwide spread of the virus, very likely from an initial African origin. (Hepatology 2017;66:1826-1841).

Niger is a west African country that is highly endemic for hepatitis B virus (HBV) infection. The seroprevalence for HBV surface antigen (HBsAg) is about 20 %; however, there are no reports on the molecular epidemiology of HBV strains spreading in Niger. In the present study, HBV isolates from the sera of 58 consecutive, asymptomatic, HBsAg-positive blood donors were characterized. Genotype affiliation was determined by amplification, sequencing and phylogenetic analysis of the preS1, polymerase/reverse transcriptase (RT/Pol) and precore (preC)/C regions. The first series of results revealed that different genomic fragments clustered with different genotypes on phylogenetic trees, suggesting recombination events. Twenty-four complete genomic sequences were obtained by amplification and sequencing of seven overlapping regions covering the whole genome, and were studied by extensive phylogenetic analysis. Among them, 20 (83.3 %) were classified unequivocally as genotype E (HBV/E). The remaining four (16.7%) clustered on a distinct branch within HBV/D with strong bootstrap and posterior probability values. Complete molecular characterization of these four strains was achieved by the Simplot program, bootscanning analysis and cloning experiments, and enabled us to identify an HBV/D-E recombinant that formed a new HBV/D subgenotype spreading in Niger, tentatively named D8. Moreover, 20 new complete HBV/E nucleotide sequences were determined that exhibited higher genetic variability than is generally described in Africa. One was found to be a recombinant containing HBV/D sequences in the preS2 and RT/Pol regions. Taken together, these data suggest that, in Niger, genetic variability of HBV strains is still evolving, probably reflecting ancient endemic HBV infection. INTRODUCTIONHepatitis B virus (HBV) infection remains a major public health problem, particularly in Africa, although data for precisely estimating the burden of HBV infection are lacking. It is estimated that 2 billion people worldwide are or have been infected with HBV (WHO: http://www.who. int/csr/disease/hepatitis/HepatitisB_whocdscsrlyo2002_2.pdf), among whom over 360 million are in a chronic carrier state with a high risk of developing cirrhosis and hepatocellular carcinoma (Ganem & Prince, 2004;Lee et al., 1997;Lok, 2004). About 70-140 million of these carriers live in Africa, and about 250 000 of the 1.3 million HBV-related deaths recorded each year throughout the world occur in Africa (Andernach et al., 2009;Hubschen et al., 2008;Kramvis & Kew, 2007;Kramvis et al., 2002;Mulders et al., 2004). HBV belongs to the family Hepadnaviridae and is characterized by a partially double-stranded circular DNA genome of 3These authors contributed equally to this work.The GenBank/EMBL/DDBJ accession numbers for the sequences determined in this study are FN594748-FN594771.A supplementary list of additional GenBank sequences used in this study is available with the online version of this paper. RESULTS Nucleotide sequences and phylogenetic analysesSeveral nucleot...

Co-infection and superinfection of hepatitis B virus (HBV) with hepatitis delta virus (HDV) leads to suppression of HBV replication both in patients and in animal and cellular models. The mechanisms behind this inhibition have not previously been explored fully. HBV replication is governed by four promoters and two enhancers, Enh1 and Enh2. Repression of these enhancers has been reported to be one of the main mechanisms of HBV inhibition. Moreover, in a previous study, it has been demonstrated that alpha interferon (IFN-a)-inducible MxA protein inhibits HBV replication. HDV encodes two proteins, p24 and p27. p27 was shown to activate several heterologous promoters, including HBV promoters. In an attempt to analyse the mechanisms of HBV inhibition by HDV, the question was raised whether HDV proteins could act directly by repressing HBV enhancers, and/or indirectly by activating the MxA gene. This issue was addressed in a co-transfection model in Huh-7 cells, using p24-or p27-expressing plasmids along with Enh1, Enh2, HBV and MxA promoter-luciferase constructs. Enh1 and Enh2 were strongly repressed, by 60 and 80 % and 40 and 60 %, by p24 and p27, respectively. In addition, p27 was responsible for threefold activation of the MxA promoter and potentiation of IFN-a on this promoter. MxA mRNA quantification and a virus yield reduction assay confirmed these results. In conclusion, this study shows that HDV proteins inhibit HBV replication by trans-repressing its enhancers and by trans-activating the IFN-a-inducible MxA gene. INTRODUCTIONChronic hepatitis B virus (HBV) infection is an important worldwide cause of acute and end-stage liver diseases, including cirrhosis and hepatocellular carcinoma. Two billion individuals have been infected with HBV and more than 400 million are chronic carriers. Hepatitis delta virus (HDV) is a naturally defective RNA virus, a satellite of HBV, which requires HBV surface antigen (HBsAg) for packaging and transmission. Between ten and twenty million HBV-infected individuals are thought to be coinfected with HDV, leading to disease chronicity and worsening histological lesions.Concomitant HBV/HDV infection often results in inhibition of HBV replication both in human patients (Arribas et al., 2005;Colombo et al., 1991;Govindarajan, 1990;Jardi et al., 2001;Lee et al., 1987;Pastore et al., 1990) and in animals (Negro et al., 1989). One in vitro transient cotransfection model of HBV DNA and HDV-expressing plasmids in Huh-7 cells has been described (Wu et al., 1991). In that study, the authors showed remarkably reduced levels of 3.5 and 2.1 kb HBV RNAs involving the delta proteins. However, the mechanisms of such inhibition remain unknown and, to our knowledge, have not been explored further. The HBV genome consists of a 3.2 kb circular, partially double-stranded DNA genome. HBV replication is governed by four promoters (pre-S, S, core and X) and two enhancer elements, Enh1 and Enh2 (Lo & Ting, 1994;Moolla et al., 2002;Park et al., 1997;Yuh & Ting, 1990). It has been hypothesized that the two...

With the introduction of more efficient treatments for hepatitis C virus (HCV), improved epidemiological information is required at the country level to allow evidence-based policymaking for elaboration of national strategies and HCV resources planning. We present a systematic review with meta-analysis of HCV seroprevalence data in adults in African countries. We conducted a systematic review of all HCV seroprevalence estimates reported in African countries from 2000 to 2014 in MEDLINE, AJOL and grey literature. We assessed studies performed in the general population and among blood donors, pregnant women and HIV-positive patients. A meta-regression analysis was used to provide adjusted estimates of HCV seroprevalence in the general adult population in each country, accounting for the heterogeneity in sample age structure and population types in the included studies. We identified 775 national-level estimations, among which 184 were included. Estimates of HCV seroprevalence were produced for 38 countries, in addition to the results from nationwide representative surveys available in Egypt and Libya. Next to Egypt, which clearly stands out, the highest levels of seroprevalence were found in Middle Africa (e.g. Cameroon, Gabon and Angola) and some West African countries (e.g. Burkina Faso, Benin), and the largest absolute numbers of infected adults were found in Nigeria, Ethiopia and Democratic Republic of Congo. This study exposes the diversity of HCV epidemiology among African countries. Egypt and several countries of West and Middle Africa present a HCV burden that will require strong governmental commitment to promote efficient preventive and curative interventions.

No recent data are available on hepatitis B virus (HBV) and hepatitis Delta virus (HDV) prevalence in Mauritania. One thousand twenty pregnant women and 946 patients visiting for routine checkups were screened for HBV and HDV infection. Demographic, epidemiological, ethnic, clinical, and biological data were recorded. HBV and HDV genotypes were determined by sequencing and phylogenetic analyses. In the pregnant women and patients cohorts, respectively, the prevalence of HBsAg (10.7% and 18.3%) and anti‐HBcAb (66.3% and 76.5%) indicated high HBV endemicity. In pregnant women, exposure to HBV was significantly associated in multivariate analysis with education level, ethnicity, blood transfusion, and occupation. HDV antibodies (HDVAb) were found in 14.7% of pregnant women. In patients, HBsAg was found less frequently in females than in males. Again in multivariate analysis, exposure to HBV was significantly correlated with gender (males), and HDVAb positivity with age and gender. The HBV DNA viral load was >3 log IU/ml in only 10.1% of pregnant women and in 17.3% of patients. HDV‐RNA was detectable in 21 (67.7%) of the 31 patients positive for HDVAb, and in 11 of the 16 pregnant women positive for HDVAb (68.8%). The most frequent HBV genotypes were: HBV/D, 53%; HBV/E, 35%; and HBV/A, 12%. Sub‐genotyping revealed HBV/D1,/D7, and the recently described/D8. HDV genotypes were: HDV‐1, 90.3% and HDV‐5, 9.7%. This study confirms the high prevalence of HBV and HDV infections in Mauritania and demonstrates the high genetic diversity of HBV in this country. J. Med. Virol. 84: 1186–1198, 2012. © 2012 Wiley Periodicals, Inc.