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Identification of mutations in the S gene of hepatitis B virus in HIV positive Mexican patients with occult hepatitis B virus infection
Affiliation:1. Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatría, CMN Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico;2. Posgrado en Biología Experimental, DCBS, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico;3. Clinica de Hepatitis, Hospital de Infectologia Centro Médico Nacional La Raza, IMSS, Mexico City, Mexico;4. Laboratorio de Fisiología Celular, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico;5. Laboratorio de Virología, Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City, Mexico;6. Departamento de Biotecnología y Bioingeniería, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (IPN), Mexico City, Mexico
Abstract:
Introduction and aimOccult hepatitis B virus infection (OBI) is characterized by the presence of replication-competent hepatitis B virus (HBV) DNA in the liver and/or serum of patients with undetectable levels of the HBV surface antigen (HBsAg). Due to the shared infection routes HIV positive patients are at higher risk of developing OBI, thus, the aim of this study was to determine the frequency of OBI in Mexican HIV-infected patients and to identify mutations in the HBV S gene that could be associated to the development of OBI.Materials and methodsPlasma samples from 50 HIV-infected patients with undetectable levels of the HBsAg were obtained and analyzed. The Core, PreS and S genes were amplified by nested PCR and sequenced by the Sanger method. To analyze HBV diversity in the OBI-positive patients, ten sequences of 762 bp from the HBV S gene were selected, cloned, and subsequently sequenced for mutational analyses.ResultsOBI infection was found with a frequency of 36% (18/50). All the HBV sequences corresponded to the H genotype. The most common mutations were: C19Y, Q129H, E164D, and I195M, with a frequency of 44%, 36%, 39% and 48% respectively.ConclusionsIn this study, we report the presence of OBI in a cohort of Mexican HIV-infected patients with an overall prevalence of 36%. Mutational analyses revealed that four non-silent mutations were frequent in different regions of the HBsAg gene, suggesting that they might be associated to the development of OBI in this population, nevertheless, further studies are required to determine their role in the pathogenesis of OBI.
Keywords:Occult hepatitis B virus infection  Hepatitis B surface antigen  Major hydrophilic region  S protein mutations  Molecular diagnostics
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