Casey J L, Brown T L, Colan E J, Wignall F S, Gerin J L
Department of Microbiology, Georgetown University School of Medicine, Rockville, MD 20852.
Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9016-20. doi: 10.1073/pnas.90.19.9016.
Hepatitis D virus (HDV) is the cause of an unusually severe form of liver disease with distinct histologic features (morula cell) that occurs throughout northern South America and certain other areas of the world. Clinical studies of HDV disease worldwide indicate that there is, in fact, a wide variation in pathogenesis, and the reasons for these differences are presently unknown. One possible explanation is that factors associated with the viral genotype are determinants of HDV pathogenesis. In this study, nucleic acid sequences were determined for three different northern South American HDV isolates which were obtained from individuals with severe disease or a family history of severe disease, in areas that are hyperendemic for this disease pattern. The sequences of these three isolates are very similar to one another but only distantly related to other published HDV sequences. Comparison of the sequence of a semiconserved region from a total of 14 isolates indicates that there are at least three HDV genotypes. Most published HDV sequences, including those from North America, Europe, the Middle East, the South Pacific, and Asia, belong to a single genotype which may have some geographically based subtypes. A single Japanese isolate is the sole representative of a second HDV genotype. The South American sequences reported here constitute a third genotype. The association of a particular genotype with the severe form of type D hepatitis that occurs in northern South America supports the hypothesis that HDV genetic factors are important determinants in the pathogenesis of type D hepatitis.
丁型肝炎病毒(HDV)是一种导致肝脏疾病的病因,这种疾病异常严重,具有独特的组织学特征(桑椹状细胞),在南美洲北部及世界其他某些地区均有发生。全球范围内对HDV疾病的临床研究表明,实际上其发病机制存在很大差异,而造成这些差异的原因目前尚不清楚。一种可能的解释是,与病毒基因型相关的因素是HDV发病机制的决定因素。在本研究中,测定了来自南美洲北部三种不同HDV分离株的核酸序列,这些分离株取自患有严重疾病或有严重疾病家族史的个体,来自该疾病模式高度流行的地区。这三种分离株的序列彼此非常相似,但与其他已发表的HDV序列仅有远缘关系。对总共14个分离株的一个半保守区域序列进行比较表明,至少存在三种HDV基因型。大多数已发表的HDV序列,包括来自北美、欧洲、中东、南太平洋和亚洲的序列,都属于单一基因型,该基因型可能有一些基于地理区域的亚型。一个日本分离株是第二种HDV基因型的唯一代表。这里报道的南美序列构成了第三种基因型。特定基因型与南美洲北部发生的严重丁型肝炎的关联支持了HDV遗传因素是丁型肝炎发病机制中重要决定因素的假说。