Examinando por Autor "Brahm, J."

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  • Miniatura
    Ítem
    Genomic determinants of hepatitis C virus antiviral therapy outcomes: Toward individualized treatment
    (Elsevier, 2012) Venegas, M.; Brahm, J.; Villanueva, R.
    Hepatitis C virus (HCV) is an important global health problem with an estimated prevalence of more than 170 million infected individuals worldwide. Currently, the standard antiviral therapy, based on pegylated in-terferon alpha and ribavirin, can achieve a virological response in only nearly 50% of the patients infected with HCV genotype 1, the most widely distributed globally. During the last years, relevant data from geno-me-wide association studies (GWAS) about the impact and contribution of the patient genomics on viral in-fection outcomes has suggested the possibility that an individualized antiviral therapy can be considered. In this review, we analyze the existing information on single nucleotide polymorphisms (SNPs) of several host genes and viral factors that influence, as a whole, the outcome of the standard antiviral therapy, and that might be used to predict an individualized antiviral response. We also discuss the clinical data within the most recent context of the triple antiviral therapy.
  • Miniatura
    Ítem
    The viral transactivator HBx protein exhibits a high potential for regulation via phosphorylation through an evolutionarily conserved mechanism
    (BMC, 2012) Hernández, S.; Venegas, M.; Brahm, J.; Villanueva, R.
    Hepatitis B virus (HBV) encodes an oncogenic factor, HBx, which is a multifunctional protein that can induce dysfunctional regulation of signaling pathways, transcription, and cell cycle progression, among other processes, through interactions with target host factors. The subcellular localization of HBx is both cytoplasmic and nuclear. This dynamic distribution of HBx could be essential to the multiple roles of the protein at different stages during HBV infection. Transactivational functions of HBx may be exerted both in the nucleus, via interaction with host DNA-binding proteins, and in the cytoplasm, via signaling pathways. Although there have been many studies describing different pathways altered by HBx, and its innumerable binding partners, the molecular mechanism that regulates its different roles has been difficult to elucidate. Methods. In the current study, we took a bioinformatics approach to investigate whether the viral protein HBx might be regulated via phosphorylation by an evolutionarily conserved mechanism. Results: We found that the phylogenetically conserved residues Ser25 and Ser41 (both within the negative regulatory domain), and Thr81 (in the transactivation domain) are predicted to be phosphorylated. By molecular 3D modeling of HBx, we further show these residues are all predicted to be exposed on the surface of the protein, making them easily accesible to these types of modifications. Furthermore, we have also identified Yin Yang sites that might have the potential to be phosphorylated and O-β-GlcNAc interplay at the same residues. Conclusions: Thus, we propose that the different roles of HBx displayed in different subcellular locations might be regulated by an evolutionarily conserved mechanism of posttranslational modification, via phosphorylation.