Chronic infection by either hepatitis B virus (HBV) or hepatitis C virus (HCV) share epidemiological characteristics with risks for development of severe complications such as liver cirrhosis and hepatocellular carcinoma. HBV and HCV also share a high genetic variability. Among highly variable regions, viral genes encoding surface proteins (hepatitis B surface antigen, E1/E2 HCV glycoproteins) play key roles in the stimulation of the host-related immune response and viral entry into hepatocytes. Specific segments of HBV envelope proteins (preS1, "a" determinant) are crucial in the entry process into permissive cells. HCV entry is a complex multistep process involving multiple cell cofactors (glycosaminoglycans, low density lipoprotein receptor, SR-B1, CD81, claudin-1, occludin, EGFR, EphA2) in the interaction with HCV E1/E2 envelope glycoproteins. In vitro both viruses can be controlled by antibody-mediated neutralization targeting viral envelope, also essential in preventing HBV infection in vivo as observed through successful vaccination using HBs antigen. But preventive vaccination and/or therapeutic pressure can influence HBV and HCV variability. For HBV, the patterns of antiviral drug resistance in chronic hepatitis are complex and the original pol/S gene overlap has to be taken into account. Treatment-induced HBV mutations in pol could indeed generate S mutants with subsequent modified antigenicity or increased cancer induction. Variability of HBV and HCV envelope proteins combining high exposure to selective pressures and crucial functional roles require investigation in the context of diagnostic, vaccination and treatment tools. In this editorial a synthesis is performed of HBV and HCV envelope properties at the entry step and as antigenic proteins, and the subsequent clinical impact.
A major challenge for antiviral treatment of hepatitis C virus (HCV) infection is viral resistance, potentially resulting from the high variability of HCV envelope glycoproteins and subsequent selection of strains with enhanced infectivity and/or immune escape.
The poor response to the combined antiviral therapy of pegylated alfa-interferon and ribavarin for hepatitis C virus (HCV) infection may be linked to mutations in the viral envelope gene E1E2 (env), which can result in escape from the immune response and higher efficacy of viral entry. Mutations that result in failure of therapy most likely require compensatory mutations to achieve sufficient change in envelope structure and function. Compensatory mutations were investigated by determining positions in the E1E2 gene where amino acids (aa) covaried across groups of individuals. We assessed networks of covarying positions in E1E2 sequences that differentiated sustained virological response (SVR) from non-response (NR) in 43 genotype 1a (17 SVR), and 49 genotype 1b (25 SVR) chronically HCV-infected individuals. Binary integer programming over covariance networks was used to extract aa combinations that differed between response groups. Genotype 1a E1E2 sequences exhibited higher degrees of covariance and clustered into 3 main groups while 1b sequences exhibited no clustering. Between 5 and 9 aa pairs were required to separate SVR from NR in each genotype. aa in hypervariable region 1 were 6 times more likely than chance to occur in the optimal networks. The pair 531-626 (EI) appeared frequently in the optimal networks and was present in 6 of 9 NR in one of the 1a clusters. The most frequent pairs representing SVR were 431-481 (EE), 500-522 (QA) in 1a, and 407-434 (AQ) in 1b. Optimal networks based on covarying aa pairs in HCV envelope can indicate features that are associated with failure or success to antiviral therapy.
We evaluated the performance of the BACTEC Peds Plus bottles for the detection of bacteria in 186 tissue samples obtained from orthopedic infections. BACTEC Peds Plus bottles led to bacterial detection in 69% of these samples against less than 53% for each of the other types of conventional media (P < 0.05). For some patients, the time of detection of pathogens was lower with the BACTEC Peds Plus bottles than with the conventional media.
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