Stamey F R, Dominguez G, Black J B, Dambaugh T R, Pellett P E
Centers for Disease Control and Prevention, Atlanta, Georgia 30333.
J Virol. 1995 Jan;69(1):589-96. doi: 10.1128/JVI.69.1.589-596.1995.
We identified some passage lineages of human herpesvirus 6 variant B (HHV-6B) strain Z29 that contain as many as 12 tandem copies of a genomic segment that corresponds almost precisely to a previously identified minimal efficient origin of lytic replication (oriLyt). Analysis of nucleotide sequences in the vicinity of the amplified segment suggests that the amplification occurred as a two-step process, with the first step being a rare sequence duplication mediated through directly repeated sequences located near the termini of the amplified segment and the second step occurring via homologous recombination through the duplicated sequence. These results demonstrate that oriLyt has been amplified in some virus stocks and indicate that (i) origin amplification confers a growth advantage on the virus in cell culture and (ii) laboratory-passaged HHV-6B genomes can accommodate additional nucleotide sequences and thus may be useful gene transfer vectors. The structures of the amplified segment and its adjacent sequences together suggest that HHV-6B or a progenitor virus acquired oriLyt by transposition from an unknown source.
我们鉴定出了人类疱疹病毒6型B亚型(HHV-6B)Z29株的一些传代谱系,这些谱系含有多达12个串联拷贝的基因组片段,该片段几乎精确对应于先前鉴定的裂解复制最小有效起始点(oriLyt)。对扩增片段附近核苷酸序列的分析表明,扩增是一个两步过程,第一步是通过位于扩增片段末端附近的直接重复序列介导的罕见序列重复,第二步是通过重复序列的同源重组发生的。这些结果表明oriLyt在一些病毒株中发生了扩增,并表明(i)起始点扩增赋予病毒在细胞培养中的生长优势,以及(ii)实验室传代的HHV-6B基因组可以容纳额外的核苷酸序列,因此可能是有用的基因转移载体。扩增片段及其相邻序列的结构共同表明,HHV-6B或其祖病毒通过从未知来源的转座获得了oriLyt。