Composition pour Le grain de riz

This is a written assignment related to the short story Le grain de riz (Gaussel, Alain)

The Core/E1 domain of Hepatitis C virus genotype 4a in Egypt does not contain viral mutations or strains specific for hepatocellular carcinoma

[EN] Background: Hepatitis C virus (HCV) infection is a well-documented etiological factor for hepatocellular carcinoma (HCC). As HCV shows remarkable genetic diversity, an interesting and important issue is whether such a high viral genetic diversity plays a role in the incidence of HCC. Prior data on this subject are conflicting. Objectives: Potential association between HCV genetic mutations or strain variability and HCC incidence has been examined through a comparative genetic analysis merely focused on a single HCV subtype (genotype 4a) in a single country (Egypt). Study design: The study focused on three HCV sequence datasets with explicit sampling dates and disease patterns. An overlapping HCV Core/E1 domain from three datasets was used as the target for comparative analysis through genetic and phylogenetic approaches. Results: Based on partial Core/E1 domain (387 bp), genetic and phylogenetic analysis did not identify any HCC-specific viral mutations and strains, respectively. Conclusions: The Core/E1 domain of HCV genotype 4a in Egypt does not contain HCC-specific mutations or strains. Additionally, sequence errors resulting from the polymerase chain reaction, together with a strong evolutionary pressure on HCV in patients with end-stage liver disease, have significant potential to bias data generation and interpretation. (C) 2011 Elsevier B.V. All rights reserved.This work was supported by NIH grants R01 DK80711 (Dr. Xiaofeng Fan), R21 AI076834 (Dr. Adrian M. Di Bisceglie) and USA and Egypt Science and Technology Joint Fund BIO6-002-004 (Dr. Adrian M. Di Bisceglie).Zhang, X.; Ryu, SH.; Xu, Y.; Elbaz, T.; Zekri, AN.; Abdelaziz, AO.; Abdel-Hamid, M.... (2011). The Core/E1 domain of Hepatitis C virus genotype 4a in Egypt does not contain viral mutations or strains specific for hepatocellular carcinoma. Journal of Clinical Virology. 52(4):333-338. https://doi.org/10.1016/j.jcv.2011.08.022S33333852

Phylogenetic analysis of hepatitis C virus isolates from Tunisian patients.

International audienceThere is little information on the epidemiology characterisation of HCV isolates in Tunisia. Previous report showed predominance of genotype 1b. In this study, 32 HCV isolates from genotypes 1a (n = 10), 1b (n = 14), 2 (n = 4), 3a (n = 3) and 4 (n = 1) were genotyped by sequencing and phylogenetic analysis on the non-structural 5b (NS5b) region. The isolates originated from 14 patients with chronic hepatitis, 10 haemophiliacs and eight healthy blood donors. NS5b sequence grouping was concordant with previous 5' untranslated region (5'UTR) genotyping results in 91% of cases. Most of the Tunisian isolates were closely related to the European ones, except for genotype 4 which seems to be related mostly to isolates from Egypt. Isolates from genotype 1a obtained from haemophiliacs showed distinct clustering and nucleic divergence from those obtained from non-haemophiliac patients, this underlines the particular mode of contamination of this group of patients

Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage

International audienceForeign and self-cytoplasmic DNA are recognized by numerous DNA sensor molecules leading to the production of type I interferons. Such DNA ago-nists should be degraded otherwise cells would be chronically stressed. Most human APOBEC3 cytidine deaminases can initiate catabolism of cytoplasmic mitochondrial DNA. Using the human myeloid cell line THP-1 with an interferon inducible APOBEC3A gene, we show that cytoplasmic DNA triggers inter-feron and production through the RNA poly-merase III transcription/RIG-I pathway leading to massive upregulation of APOBEC3A. By catalyzing C→U editing in single stranded DNA fragments, the enzyme prevents them from re-annealing so attenuating the danger signal. The price to pay is chromo-somal DNA damage in the form of CG→TA mutations and double stranded DNA breaks which, in the context of chronic inflammation, could drive cells down the path toward cancer

Methylglyoxal induces advanced glycation end product (AGEs) formation and dysfunction of PDGF receptor-beta: implications for diabetic atherosclerosis.

International audiencePURPOSE: Low molecular weight carbonyl compounds, such as the alpha-ketoaldehydes methylglyoxal (MGO) and glyoxal (GO), are formed under hyperglycemic conditions and behave as advanced glycation end product (AGE) precursors. They form adducts on proteins, thereby inducing cellular dysfunctions involved in chronic complications of diabetes. METHODS AND MAIN FINDINGS: Nontoxic concentrations of GO or MGO altered the PDGF-induced PDGFRbeta-phosphorylation, ERK1/2-activation, and nuclear translocation, and the subsequent proliferation of mesenchymal cells (smooth muscle cells and skin fibroblasts). This resulted mainly from inhibition of the intrinsic tyrosine kinase of PDGFRbeta and in part from altered PDGF-BB binding to PDGFRbeta. Concomitantly, the formation of AGE adducts (N(epsilon)carboxymethyl-lysine and N(epsilon)carboxyethyl-lysine) was observed on immunoprecipitated PDGFRbeta. Arginine and aminoguanidine, used as carbonyl scavengers, reversed the inhibitory effect and the formation of AGE adducts on PDGFRbeta. AGE-PDGFRbeta adducts were also detected by anti-AGE antibodies in PDGFRbeta immunopurified from aortas of diabetic (streptozotocin-treated) compared to nondiabetic apolipoprotein E-null mice. Mass spectrometry analysis of aortas demonstrated increased AGE formation in diabetic specimens. CONCLUSIONS: These data indicate that MGO and GO induce desensitization of PDGFRbeta that helps to reduce mesenchymal cell proliferation

Change in hepatitis C virus genotype in hemodialysis patients after end-of-treatment response to interferon monotherapy--relapse or re-infection?

Hepatitis C virus (HCV) infection remains common among hemodialysis patients and its occurrence is related mainly to nosocomial spread. Although dialysis patients with HCV infection respond well to interferon-based therapy, relapse is frequent. This study aimed at a selected group of hemodialysis patients infected with HCV infection undergoing interferon therapy who achieved end-of-treatment virological response but became HCV-RNA positive again 6 months after end-of-treatment. It was evaluated whether de novo HCV-RNA positivity in these non-sustained responders occurred due to lack of clearance of HCV after the initial response to interferon-alpha (relapse) or due to re-infection with a new strain (re-infection). Genotyping by Inno-LiPA and by phylogenetic tree analysis using partial HCV-NS5B sequences at two evaluation points: pre-treatment (T0) and 6 months after end-of-treatment (T18). Non-sustained responders (n = 15) carried subtypes 1a (8 patients), 1b (4 patients), 3a (2 patients), and 4a (1 patient) before treatment. Identical subtypes were detected in 10 patients at T18. Five patients changed genotypes at T18, suggesting nosocomial re-infection. This study emphasizes the importance of epidemiologic measures to control the re-exposure of hemodialysis patients treated previously for HCV infection.status: publishe

Intrahepatic hepatitis C virus RNA quantification in microdissected hepatocytes

International audienceBackground/Aims: Debate continues on whether serum and intrahepatic HCV viral loads are correlated and if HCV viral load correlates with the severity of liver disease. These difficulties may at least in part be linked to liver cell heterogeneity, when total liver extracts from HCV-infected individuals are tested for HCV RNA quantification. We have therefore investigated the feasibility of quantifying HCV replication using a laser-based microdissection technique.Methods: We compared the results with those obtained for serum HCV RNA quantification and immunochemistry in the case of HCV antigen detection in the liver. Twenty-one HCV-positive patients with chronic active hepatitis (n=10) or cirrhosis (n=11) were analyzed.Results: A positive correlation (P=0.0019) was observed between HCV RNA quantifications in sera and microdissected cells. Immunohistochemistry demonstrated that HCV antigen hepatocytes were randomly distributed within liver lobules. Their percentage varied in different patients (0–40%), but did not correlate with the HCV viral load.Conclusions: We have designed a sensitive methodology to evaluate the intrahepatic HCV viral load by combining a standardized RNA quantification method with microdissected hepatocytes from frozen liver needle biopsies. Our results directly demonstrate a positive correlation between serum and intrahepatic viral loads, which therefore provides a reliable reflection of intrahepatic HCV replication

Change in hepatitis C virus genotype in hemodialysis patients after end-of-treatment response to interferon monotherapy-relapse or re-infection?

Hepatitis C virus (HCV) infection remains common among hemodialysis patients and its occurrence is related mainly to nosocomial spread. Although dialysis patients with HCV infection respond well to interferon-based therapy, relapse is frequent. This study aimed at a selected group of hemodialysis patients infected with HCV infection undergoing interferon therapy who achieved end-of-treatment virological response but became HCV-RNA positive again 6 months after end-of-treatment. It was evaluated whether de novo HCV-RNA positivity in these non-sustained responders occurred due to lack of clearance of HCV after the initial response to interferon-alpha (relapse) or due to re-infection with a new strain (re-infection). Genotyping by Inno-LiPA and by phylogenetic tree analysis using partial HCV-NS5B sequences at two evaluation points: pre-treatment (TO) and 6 months after end-of-treatment (T0). Non-sustained responders (n = 15) carried subtypes la (8 patients), 1b (4 patients), 3a (2 patients), and 4a (11 patient) before treatment. Identical subtypes were detected in 10 patients at T18. Five patients changed genotypes at T18, suggesting nosocomial re-infection. This study emphasizes the importance of epidemiologic measures to control the re-exposure of hemodialysis patients treated previously for HCV infection.Erasmus MC, Infect Dis Virol Dept, NL-3015 CE Rotterdam, NetherlandsUniversidade Federal de São Paulo, UNIFESP, São Paulo, BrazilKatholieke Univ Leuven, Rega Inst Med Res, Louvain, BelgiumInst Pasteur, Dept Virol, Paris, FranceINSERM, U785, Villejuif, FranceUniv Paris Sud, UMR S785, Villejuif, FranceUniversidade Federal de São Paulo, UNIFESP, São Paulo, BrazilWeb of Scienc

Sustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus

International audienceAPOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens

HCV iatrogenic and intrafamilial transmission in Greater Cairo, Egypt

International audienceObjectives To document hepatitis C virus (HCV) intrafamilial transmission and assess its relative importance in comparison to other current modes of transmission in the country with the largest HCV epidemic in the world. HCV intrafamilial transmission was defined as HCV transmission among relatives living in the same household.Design Case–control study. Cases were adult patients with acute hepatitis C diagnosed in two ‘fever hospitals’ of Cairo. Controls were adult patients with acute hepatitis A diagnosed in the same two hospitals, and family members of cases. All consenting household members of cases provided blood for HCV serological and RNA testing. Homology of viral sequences (NS5b region) within households was used to ascertain HCV intrafamilial transmission. Exposures at risk for HCV during the 1–6 months previous to onset of symptoms were assessed in all cases and controls.Results From April 2002 to June 2007, 100 cases with acute hepatitis C, and 678 controls (416 household members and 262 patients with acute hepatitis A) were recruited in the study. Factors independently associated with HCV infection and their attributable fractions (AFs) were the following: having had a catheter (OR=5.0, 95% CI=1.4 to 17.8; AF=6.7%), an intravenous perfusion (OR=5.8, 95% CI=2.5 to 13.3; AF=20.1%), stitches (OR=2.0, 95% CI=1.3 to 6.6; AF=10.7%), gum treatment (OR=3.7, 95% CI=1.1 to 11.9; AF=3.8%) and being illiterate (OR=2.4, 95% CI=1.4 to 4.4). Of the 100 cases, 18 had viraemic HCV-infected household members. Three long-married (>15 years) couples were infected with virtually identical sequences and none of the three index patients reported any exposure at risk, suggesting HCV intra-familial transmission.Conclusion While three new HCV infections out of 100 could be linked to intra-familial transmission, parenteral iatrogenic transmission (dental care included) was accountable for 34.6% of these new infections. Thus, the relative contribution of intrafamilial transmission to HCV spread seems to be limited