Borkakoti Jayanta, Ahmed Giasuddin, Kar Premashis
PCR Hepatitis Laboratory, Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India; Department of Biotechnology, Gauhati University, Assam, India.
Department of Biotechnology, Gauhati University, Assam, India.
Infect Genet Evol. 2016 Oct;44:51-54. doi: 10.1016/j.meegid.2016.06.030. Epub 2016 Jun 15.
Here, we report the molecular alterations in the HEV genome from patients with acute liver failure (ALF) and acute viral hepatitis (AVH) from North India, including pregnant women and its association with the poor outcome of the disease. We partially sequenced the RNA Dependent RNA polymerase (RdRp) region of the ORF 1 protein in the HEV genome from representative samples from patients with ALF and AVH and identified two novel mutations Cysteine 1483 Tryptophan and Asparagine 1530 Threonine in 100% (25/25) of the patients with ALF compared to none (0/30) of the patients with AVH (P<0.0001). Disease severity parameters along with viral load corresponding to the samples with C1483W and N1530T mutations were significantly higher compared to those lacking the mutation showing significant association with the outcome in ALF patients. The nucleotide substitutions in the RdRp region may play a crucial role in enhancing HEV replication thus leading to disease severity.
在此，我们报告了来自印度北部急性肝衰竭（ALF）和急性病毒性肝炎（AVH）患者（包括孕妇）的戊型肝炎病毒（HEV）基因组的分子改变及其与疾病不良结局的关联。我们对来自ALF和AVH患者的代表性样本中HEV基因组的开放阅读框1（ORF1）蛋白的RNA依赖性RNA聚合酶（RdRp）区域进行了部分测序，在100%（25/25）的ALF患者中鉴定出两个新突变，即半胱氨酸1483色氨酸和天冬酰胺1530苏氨酸，而AVH患者中无一例（0/30）出现此类突变（P<0.0001）。与缺乏C1483W和N1530T突变的样本相比，具有这些突变的样本的疾病严重程度参数以及病毒载量显著更高，表明这些突变与ALF患者的结局存在显著关联。RdRp区域的核苷酸替换可能在增强HEV复制从而导致疾病严重程度方面发挥关键作用。
