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鉴定墨西哥 HIV 阳性隐匿性乙型肝炎病毒感染患者乙型肝炎病毒 S 基因中的突变。

Identification of mutations in the S gene of hepatitis B virus in HIV positive Mexican patients with occult hepatitis B virus infection.

机构信息

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; Posgrado en Biología Experimental, DCBS, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico.

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.

出版信息

Ann Hepatol. 2020 Sep-Oct;19(5):507-515. doi: 10.1016/j.aohep.2020.06.002. Epub 2020 Jun 25.

Abstract

INTRODUCTION AND AIM

Occult 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 METHODS

Plasma 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 762bp from the HBV S gene were selected, cloned, and subsequently sequenced for mutational analyses.

RESULTS

OBI 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.

CONCLUSIONS

In 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.

摘要

介绍和目的

隐匿性乙型肝炎病毒感染(OBI)的特征是在乙型肝炎病毒表面抗原(HBsAg)水平不可检测的患者的肝脏和/或血清中存在具有复制能力的乙型肝炎病毒(HBV)DNA。由于具有共同的感染途径,HIV 阳性患者发生 OBI 的风险更高,因此,本研究的目的是确定墨西哥 HIV 感染患者中 OBI 的频率,并确定与 OBI 发展相关的 HBV S 基因中的突变。

材料和方法

从 50 名 HBsAg 水平不可检测的 HIV 感染患者中获得并分析了血浆样本。通过巢式 PCR 扩增核心、前 S 和 S 基因,并通过 Sanger 法测序。为了分析 OBI 阳性患者中的 HBV 多样性,从 HBV S 基因中选择了 762bp 的十个序列进行克隆和测序,以进行突变分析。

结果

发现 OBI 感染的频率为 36%(18/50)。所有 HBV 序列均对应于 H 基因型。最常见的突变是:C19Y、Q129H、E164D 和 I195M,频率分别为 44%、36%、39%和 48%。

结论

在这项研究中,我们报告了在一组墨西哥 HIV 感染患者中存在 OBI,总体患病率为 36%。突变分析显示,HBsAg 基因不同区域的四个非沉默突变频繁出现,提示它们可能与该人群中 OBI 的发生有关,但需要进一步研究以确定它们在 OBI 发病机制中的作用。

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