High prevalence and diversity of hepatitis B and hepatitis delta virus in Gabon

International audienc

Lancet Public Health

International audienc

Tma108, a putative M1 aminopeptidase, is a specific nascent chain-associated protein in Saccharomyces cerevisiae

International audienceThe discovery of novel specific ribosome-associated factors challenges the assumption that translation relies on standardized molecular machinery. In this work, we demonstrate that Tma108, an uncharac-terized translation machinery-associated factor in yeast, defines a subpopulation of cellular ribosomes specifically involved in the translation of less than 200 mRNAs encoding proteins with ATP or Zinc binding domains. Using ribonucleoparticle dissoci-ation experiments we established that Tma108 directly interacts with the nascent protein chain. Additionally , we have shown that translation of the first 35 amino acids of Asn1, one of the Tma108 targets, is necessary and sufficient to recruit Tma108, suggesting that it is loaded early during translation. Comparative genomic analyses, molecular model-ing and directed mutagenesis point to Tma108 as an original M1 metallopeptidase, which uses its pu-tative catalytic peptide-binding pocket to bind the N-terminus of its targets. The involvement of Tma108 in co-translational regulation is attested by a drastic change in the subcellular localization of ATP2 mRNA upon Tma108 inactivation. Tma108 is a unique example of a nascent chain-associated factor with high selectivity and its study illustrates the existence of other specific translation-associated factors besides RNA binding proteins

High Prevalence and Diversity of Hepatitis Viruses in Suspected Cases of Yellow Fever in the Democratic Republic of Congo

International audienceThe majority of patients with acute febrile jaundice (>95%) identified through a yellow fever surveillance program in the Democratic Republic of Congo (DRC) test negative for antibodies against yellow fever virus. However, no etiological investigation has ever been carried out on these patients. Here, we tested for hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV) viruses, all of which can cause acute febrile jaundice, in patients included in the yellow fever surveillance program in the DRC. On a total of 498 serum samples collected from suspected cases of yellow fever from January 2003 to January 2012, enzyme-linked immunosorbent assay (ELISA) techniques were used to screen for antibodies against HAV (IgM) and HEV (IgM) and for antigens and antibodies against HBV (HBsAg and anti-hepatitis B core protein [HBc] IgM, respectively), HCV, and HDV. Viral loads and genotypes were determined for HBV and HVD. Viral hepatitis serological markers were diagnosed in 218 (43.7%) patients. The seroprevalences were 16.7% for HAV, 24.6% for HBV, 2.3% for HCV, and 10.4% for HEV, and 26.1% of HBV-positive patients were also infected with HDV. Median viral loads were 4.19 × 10 5 IU/ml for HBV (range, 769 to 9.82 × 10 9 IU/ml) and 1.4 × 10 6 IU/ml for HDV (range, 3.1 × 10 2 to 2.9 × 10 8 IU/ml). Genotypes A, E, and D of HBV and genotype 1 of HDV were detected. These high hepatitis prevalence rates highlight the necessity to include screening for hepatitis viruses in the yellow fever surveillance program in the DRC

Effect of Peg-IFN on the viral kinetics of HDV infected patients treated with bulevirtide

International audienceBackground & AimsBulevirtide is a first-in-class entry inhibitor antiviral treatment for chronic hepatitis D. The viral kinetics during bulevirtide therapy and the effect of combining bulevirtide with Peg-IFN are unknown.MethodsWe used mathematical modeling to analyze the viral kinetics in two French observational cohorts of 183 patients receiving bulevirtide with or without Peg-IFN for 48 weeks.ResultsThe efficacy of bulevirtide in blocking cell infection was estimated to 90.3%, while Peg-IFN blocked viral production with an efficacy of 92.4%, albeit with large inter-individual variabilities. The addition of Peg-IFN to bulevirtide was associated with a more rapid virological decline, with a rate of virological response (>2 log of decline or undetectability) at week 48 of 86.9% (95% PI = [79.7;95.0]), compared to 56.1% (95% PI = [46.4;66.7]) with bulevirtide only. The model was also used to predict the probability to achieve a cure of viral infection, with a rate of 8.8% (95% PI = [3.5;13.2]) with bulevirtide compared to 18.8% (95% PI = [11.6;29.0]) with bulevirtide+Peg-IFN. Mathematical modeling suggests that after 144 weks of treatment, the rates of viral cure could be 42.1% (95% PI= [33.3;52.6]) with bulevirtide and 66.7% (95% PI= [56.5;76.8]) with bulevirtide+Peg-IFN.ConclusionsIn this analysis of real-world data, Peg-IFN strongly enhanced the kinetics of viral decline in patients treated with bulevirtide. Randomized clinical trials are warranted to assess the virological and clinical benefit of this combination, and to identify predictors of poor response to treatment.Impact and ImplicationBulevirtide has been approved for Chronic HDV infection by regulatory agencies in Europe based on its good safety profile and rapid virological response after treatment initiation, but the optimal duration of treatment and the chance to achieve a sustained virological response remain unknown. The results presented in this study have a high impact for clinicians and investigators as they provide important knowledge on the long-term virological benefits of a combination of peg-IFN and bulevirtide in CHD patients. Clinical trials are now warranted to confirm those predictions