Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS, USA.
Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC, USA.
Virology. 2019 May;531:100-113. doi: 10.1016/j.virol.2019.03.002. Epub 2019 Mar 4.
Mechanisms mediating clearance of hepatitis delta virus (HDV) are poorly understood. This study analyzed in detail profound down-regulation of HDV infection in the woodchuck model. Super-infection with HDV of woodchucks chronically infected with HBV-related woodchuck hepatitis virus produced two patterns. In the first, HDV viremia had a sharp peak followed by a considerable decline, and initial rise of HDV virions' infectivity followed by abrupt infectivity loss. In the second, HDV titer rose and later displayed plateau-like profile with high HDV levels; and HDV infectivity became persistently high when HDV titer reached the plateau. The infectivity loss was not due to defects in the virions' envelope, binding to anti-envelope antibodies, or mutations in HDV genome, but it correlated with profound reduction of the replication capacity of virion-associated HDV genomes. Subsequent finding that in virions with reduced infectivity most HDV RNAs were not full-length genomes suggests possible HDV clearance via RNA fragmentation.
介导清除乙型肝炎 delta 病毒 (HDV) 的机制尚不清楚。本研究详细分析了土拨鼠模型中 HDV 感染的深度下调。HBV 相关土拨鼠肝炎病毒慢性感染的土拨鼠的 HDV 超感染产生了两种模式。在第一种模式中，HDV 血症出现急剧高峰，随后显著下降，HDV 病毒粒子的感染性最初上升，随后突然丧失感染性。在第二种模式中，HDV 滴度升高，随后呈平台样特征，HDV 水平较高；当 HDV 滴度达到平台时，HDV 感染性持续升高。这种感染性丧失不是由于病毒包膜的缺陷、与包膜抗体结合或 HDV 基因组的突变，而是与病毒相关的 HDV 基因组复制能力的深刻降低相关。随后发现，在感染性降低的病毒中，大多数 HDV RNA 不是全长基因组，这表明可能通过 RNA 片段化清除 HDV。
