Casey J L
Division of Molecular Virology and Immunology, Georgetown University Medical Center, Washington, DC, USA.
Clin Lab Med. 1996 Jun;16(2):451-64.
After the discovery of HDV there have been significant advances in the understanding of the biology and disease of HDV infection. Analyses at the molecular level have revealed several fascinating features (ribozyme activity, RNA-dependent RNA polymerase activity of RNA polymerase II, HDAg isoprenylation, and RNA editing) that are of significant interest. Intensive investigation of the ribozyme elements has yielded important insights in both functional and structural features. However, there is information lacking about other aspects of the HDV replication cycle including the specific nature of the interaction between HDAg and HDV RNA, the function of HDAg in HDV RNA replication, transcription by RNA polymerase II, and the mechanisms of HDV RNA editing and its regulation. Further study of these and other aspects of the HDV replication cycle will continue to enrich our understanding of basic biology. Evaluation of the mechanisms of HDV disease remains an important goal in the study of this agent. Although both acute and chronic disease are commonly associated with unfavorable outcomes, it is clear that chronic infection is associated with a broad spectrum of disease. The interactions between HDV, HBV, and the host are necessarily complex, and it is likely that each contribute factors that influence disease and outcome. Recent analyses of HDV genotypes have suggested that disease variations may be associated with viral genetic factors. Consistent with the obligate role of HBV in the HDV life cycle, HBV replication is also an important determinant of HDV disease. It is still unclear if interactions between specific genotypes or variants of HBV and HDV influence disease. Recent data also suggest that infection with multiple hepatitis viruses (HBV, HDV, and HCV) can influence the severity of disease. It remains to be seen whether coinfection with the recently discovered hepatitis G virus is associated with altered disease patterns. Further advances in our understanding HDV disease and possible therapeutic approaches will rely on a combination of additional studies at the molecular, genetic, epidemiologic, and clinical levels. These studies will continue to elaborate the model of HDV infection and disease that can ultimately be tested by experimental infection of chimpanzees and woodchucks.
丁型肝炎病毒（HDV）被发现后，人们对HDV感染的生物学特性和疾病的认识有了显著进展。分子水平的分析揭示了几个有趣的特征（核酶活性、RNA聚合酶II的RNA依赖性RNA聚合酶活性、丁型肝炎抗原（HDAg）的异戊二烯化以及RNA编辑），这些特征备受关注。对核酶元件的深入研究在功能和结构特征方面都取得了重要见解。然而，关于HDV复制周期的其他方面仍缺乏信息，包括HDAg与HDV RNA之间相互作用的具体性质、HDAg在HDV RNA复制中的功能、RNA聚合酶II的转录以及HDV RNA编辑及其调控机制。对HDV复制周期的这些及其他方面的进一步研究将不断丰富我们对基础生物学的理解。评估HDV疾病的机制仍然是对该病原体研究的一个重要目标。虽然急性和慢性疾病通常都与不良后果相关，但很明显，慢性感染与广泛的疾病有关。HDV、乙肝病毒（HBV）与宿主之间的相互作用必然很复杂，而且它们可能各自都对影响疾病和结局的因素有贡献。最近对HDV基因型的分析表明，疾病差异可能与病毒遗传因素有关。与HBV在HDV生命周期中的必需作用一致，HBV复制也是HDV疾病的一个重要决定因素。目前尚不清楚HBV的特定基因型或变体与HDV之间的相互作用是否会影响疾病。最近的数据还表明，感染多种肝炎病毒（HBV、HDV和丙肝病毒（HCV））会影响疾病的严重程度。与最近发现的庚型肝炎病毒合并感染是否会改变疾病模式还有待观察。我们对HDV疾病及可能的治疗方法的理解取得进一步进展将依赖于在分子、遗传、流行病学和临床水平上进行更多研究的结合。这些研究将不断完善HDV感染和疾病的模型，最终可通过对黑猩猩和土拨鼠进行实验性感染来验证。
