Advanced Molecular Surveillance of Hepatitis C Virus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Recombinant hepatitis C virus-envelope protein 2 interactions with low-density lipoprotein/CD81 receptors

Hepatitis C virus (HCV) envelope protein 2 (E2) is involved in viral binding to host cells. The aim of this work was to produce recombinant E2B and E2Y HCV proteins in Escherichia coli and Pichia pastoris, respectively, and to study their interactions with low-density lipoprotein receptor (LDLr) and CD81 in human umbilical vein endothelial cells (HUVEC) and the ECV304 bladder carcinoma cell line. To investigate the effects of human LDL and differences in protein structure (glycosylated or not) on binding efficiency, the recombinant proteins were either associated or not associated with lipoproteins before being assayed. The immunoreactivity of the recombinant proteins was analysed using pooled serum samples that were either positive or negative for hepatitis C. The cells were immunophenotyped by LDLr and CD81 using flow cytometry. Binding and binding inhibition assays were performed in the presence of LDL, foetal bovine serum (FCS) and specific antibodies. The results revealed that binding was reduced in the absence of FCS, but that the addition of human LDL rescued and increased binding capacity. In HUVEC cells, the use of antibodies to block LDLr led to a significant reduction in the binding of E2B and E2Y. CD81 antibodies did not affect E2B and E2Y binding. In ECV304 cells, blocking LDLr and CD81 produced similar effects, but they were not as marked as those that were observed in HUVEC cells. In conclusion, recombinant HCV E2 is dependent on LDL for its ability to bind to LDLr in HUVEC and ECV304 cells. These findings are relevant because E2 acts to anchor HCV to host cells; therefore, high blood levels of LDL could enhance viral infectivity in chronic hepatitis C patients.

Evaluation of canonical siRNA and dicer substrate RNA for inhibition of hepatitis C virus genome replication: a comparative study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hepatitis C virus and dental health workers: an update

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação de polimorfismos genéticos na progressão da infecção de pacientes monoinfectados e coinfectados com os Vírus da Imunodeficiência Humana (HIV) e Vírus da Hepatite C (VHC)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Epidemiologia molecular do vírus da Hepatite C: análise comparativa de diferentes regiões subgenômicas aplicadas a estudos de associação genética

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Epidemiological profile of hepatitis C virus infection in patients from west region of Minas Gerais State, Brazill

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Hepatitis C infection: challenges in dental management and diagnosis of extrahepatic manifestations

Hepatitis C is associated with autoimmune diseases, hepatocellular carcinoma,and extrahepatic manifestations that, in conjunction, may seriously compromise the patient's quality of life. We herein describe a case of chronic hepatitis C with oral manifestations and discuss some implications for diagnosis and treatment. A 63-year-old woman complaining of spontaneous bleeding of the oral mucosa presented with bilateral asymmetric ulcers surrounded by white papules and striae on the buccal mucosa. Her medical history revealed leucopenia, thrombocytopenia, and skin lesions associated with chronic hepatitis C. Propranolol and ranitidine had recently been prescribed. Lichen planus, lichenoid reaction, and erythema multiforme were considered in the differential diagnosis. Histopathological analysis revealed lymphocytic infiltrate in a lichenoid pattern. The lesions partially healed after 1 week and completely regressed after 6 months, despite the maintenance of all medications; no recurrence was observed. The final diagnosis was oral lichen planus associated with hepatitis C. Chronic hepatitis C may present oral manifestations, which demand adjustments in dental treatment planning. Medication side effects may interfere with the clinical presentation and course of the disease and should be accounted for in the differential diagnosis. The possibility of spontaneous remission of oral lichen planus should always be considered, especially when putative etiological factors of a lichenoid lesion are withdrawn in an attempt to differentiate oral lichen planus from lichenoid lesions. This case emphasizes the importance of recognizing the extrahepatic manifestations of hepatitis C as a cause of increased morbidity.

Análise do efeito in vitro de acridonas na replicação do Vírus da Hepatite C

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Perfil de mutações e resistência do Vírus da Imunodeficiência Humana (HIV) em pacientes coinfectados com o Vírus da Hepatite B (VHB)

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Re-treatment of previous non-responders and relapsers to interferon plus ribavirin with peginterferon alfa-2a (40KD), ribavirin +/- amantadine in patients with chronic hepatitis C: randomized multicentre clinical trial

Introduction. A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care (pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after 24 weeks of treatment with conventional interferon plus ribavirin. Material and methods. Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (401(D) 180 pg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin). Results. The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (< 50 IU/mL) at end of follow-up (week 72). Among patients with a previous non-response, 12/53 (22.6%; 95% confidence interval [CI] 12.3-36.2%) randomized to triple therapy achieved an SVR compared with 16/52 (30.8%; 95% CI 18.7-45.1%) randomized to the standard of care. Among patients with a previous relapse 22/39 (56.4%; 95% CI 39.6-72.2%) randomized to triple therapy achieved an SVR compared with 23/38 (60.5%; 95% CI 43.4-76.0%) randomized to the standard of care. Undetectable HCV RNA (< 50 IU/mL) at week 12 had a high positive predictive value for SVR. A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin. Conclusion. Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting.

Interação entre Citocinas, Plaquetas e Fibrogênese na Investigação da Metaplasia Mielóide Hepática

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Avaliação da infecção de megacariócitos e plaquetas pelo VHC e sua influência na fisiopatologia da hepatite C

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB