ROLE OF 2 FORMS OF HEPATITIS DELTA VIRUS-ANTIGEN - EVIDENCE FOR A MECHANISM OF SELF-LIMITING GENOME REPLICATION
ROLE OF 2 FORMS OF HEPATITIS DELTA VIRUS-ANTIGEN - EVIDENCE FOR A MECHANISM OF SELF-LIMITING GENOME REPLICATION
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DOI：
10.1128/jvi.64.10.5066-5069.1990
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发表时间：
1990-10-01
影响因子：
5.4
通讯作者：
TAYLOR, J
中科院分区：
文献类型：
--
作者：
CHAO, M;HSIEH, SY;TAYLOR, J
丁型肝炎病毒的RNA基因组的复制由于存在唯一已知的病毒编码蛋白--如果不是全部的话，大多数感染的特征在于存在两种电泳形式的δ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δ抗原的功能。我们发现，只有小形式的δ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阻遏物。这种抑制是有效的。例如，当只有10%的δ抗原以大的形式存在时，基因组复制的量减少了8倍。我们的结果的一种解释是，δ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，无论是在培养细胞中的基因组复制过程中，还是在动物感染过程中，大的形式的合成可能会抑制δ复制，可能导致自限性感染。
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.