Ayari Rym, Lakhoua-Gorgi Yousr, Bouslama Lamjed, Safar Imen, Kchouk Fatma Houissa, Aouadi Houda, Jendoubi-Ayed Saloua, Najjar Taoufik, Ayed Kaled, Abdallah Taieb Ben
Laboratory of Immunology Research Center, Kidney Transplantation and Immunopathology, Charles Nicolle Hospital, University of Tunis El Manar, Tunis, Tunisia.
Hepat Mon. 2012 Nov;12(11):e6191. doi: 10.5812/hepatmon.6191. Epub 2012 Nov 30.
In this study, we evaluated the prevalence of the most common mutations occurring in Enhancer II (EnhII), Basal Core Promoter (BCP), Precore (PC), and Core (C) regions of hepatitis B virus (HBV) genome.
We also investigated the correlation between HBV variants, their genotypes, and patients' HBe antigen (HBeAg: soluble shape of the capsid antigen) status.
We retrieved viral DNA from 40 serum samples of Tunisian patients positive for hepatitis B surface antigen (HBsAg) and HBV DNA, amplified the above mentioned regions using specific primers, and sequenced the corresponding PCR (polymerase chain reaction) products. For further analysis purpose, the patients were divided into two groups: Group1 including 34 HBeAg-negative patients and Group2 with 6 HBeAg-positive patients.
Twenty-one patients (52.5%) showed PC G1896A mutation and 11 (27.5%) carried A1762T/G1764A double mutations. These mutations were more frequent in HBeAg-negative patients than that in HBeAg-positive ones. Indeed, 58.8% of patients bearing G1896A mutation were HBeAg-negative while 16.7% were positive. In patients bearing T1762/A1764 double mutation, 29.4% were positive and 16.7% were negative. In addition, the A1896 mutation was restricted to HBV isolates that had wild-type T1858, while C1858 was rather linked to the occurrence of T1762/A1764 mutation. Interestingly, this study revealed a high frequency of genotype E. This frequency was important as compared to that of genotype D known to be predominant in the country as delineated in previous studies.
Previous results supported and showed that HBV strains present in Tunisia belonging to genotype D and, to a lesser extent, to genotype E, were prone to mutations in BCP/ PC regions. This observation was more obvious in HBV isolates from asymptomatic chronic carriers (AsC). The high mutational rates observed in our study might result from a mechanism of viral escape that plays an important role in the loss of HBeAg.
在本研究中，我们评估了乙型肝炎病毒（HBV）基因组增强子II（EnhII）、基础核心启动子（BCP）、前核心（PC）和核心（C）区域中最常见突变的流行情况。
我们还研究了HBV变异体、其基因型与患者HBe抗原（HBeAg：衣壳抗原的可溶性形式）状态之间的相关性。
我们从40例乙型肝炎表面抗原（HBsAg）和HBV DNA阳性的突尼斯患者的血清样本中提取病毒DNA，使用特异性引物扩增上述区域，并对相应的聚合酶链反应（PCR）产物进行测序。为了进一步分析，患者被分为两组：第1组包括34例HBeAg阴性患者，第2组有6例HBeAg阳性患者。
21例患者（52.5%）出现PC G1896A突变，11例（27.5%）携带A1762T/G1764A双突变。这些突变在HBeAg阴性患者中比在HBeAg阳性患者中更常见。确实，携带G1896A突变的患者中58.8%为HBeAg阴性，而16.7%为阳性。在携带T1762/A1764双突变的患者中，29.4%为阳性，16.7%为阴性。此外，A1896突变仅限于具有野生型T1858的HBV分离株，而C1858则与T1762/A1764突变的发生相关。有趣的是，本研究揭示了基因型E的高频率。与先前研究中该国已知占主导地位的基因型D相比，该频率较高。
先前的结果支持并表明，突尼斯存在的HBV毒株属于基因型D，在较小程度上属于基因型E，易于在BCP/PC区域发生突变。这一观察结果在无症状慢性携带者（AsC）的HBV分离株中更为明显。我们研究中观察到的高突变率可能是由病毒逃逸机制导致的，该机制在HBeAg的丧失中起重要作用。
