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两种形式的丁型肝炎病毒抗原的作用:自我限制基因组复制机制的证据。

Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of self-limiting genome replication.

作者信息

Chao M, Hsieh S Y, Taylor J

机构信息

Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.

出版信息

J Virol. 1990 Oct;64(10):5066-9. doi: 10.1128/JVI.64.10.5066-5069.1990.

DOI:10.1128/JVI.64.10.5066-5069.1990
PMID:2398535
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC247998/
Abstract

The replication of the RNA genome of hepatitis delta virus is greatly facilitated by the presence of the only known virus-coded protein, the delta antigen. Most, if not all, infections are characterized by the presence of two electrophoretic forms of the delta antigen. These forms correspond to polypeptide lengths of 195 and 214 amino acids which are encoded by genomes with different nucleotide sequences. We used cDNA transfections to investigate the functions of these two forms of the delta antigen. We found that only the small form of delta antigen supported hepatitis delta virus genome replication and that the large form acted as a dominant negative repressor of such replication. This inhibition was potent. For example, the amount of genome replication was reduced eightfold when as little as 10% of the delta antigen was present as the large form. One interpretation of our results is that the delta antigen normally functions as part of a multimeric structure. In addition, our data suggest that synthesis of the large form, either during genome replication in cultured cells or even during infection in animals, may suppress delta replication, possibly leading to a self-limiting infection.

摘要

丁型肝炎病毒RNA基因组的复制在唯一已知的病毒编码蛋白——丁型抗原的存在下得到极大促进。大多数(即便不是全部)感染的特征是存在两种电泳形式的丁型抗原。这些形式对应于由具有不同核苷酸序列的基因组编码的195和214个氨基酸的多肽长度。我们使用cDNA转染来研究这两种形式的丁型抗原的功能。我们发现只有小形式的丁型抗原支持丁型肝炎病毒基因组复制,而大形式作为这种复制的显性负性抑制剂起作用。这种抑制作用很强。例如,当仅10%的丁型抗原以大形式存在时,基因组复制量减少了八倍。我们结果的一种解释是丁型抗原通常作为多聚体结构的一部分发挥作用。此外,我们的数据表明,在培养细胞的基因组复制过程中甚至在动物感染期间合成的大形式可能会抑制丁型复制,这可能导致自限性感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2763/247998/13d28bae2a5f/jvirol00065-0476-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2763/247998/13d28bae2a5f/jvirol00065-0476-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2763/247998/13d28bae2a5f/jvirol00065-0476-a.jpg

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Hepatitis Delta Infection: A Clinical Review.丁型肝炎病毒感染:临床综述。
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Diagnosis of HDV: From virology to non-invasive markers of fibrosis.丁型肝炎病毒的诊断:从病毒学到纤维化的非侵入性标志物。
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Hepatitis Delta: Current Knowledge and Future Directions.丁型肝炎:当前认知与未来方向。
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