霊長類全血血栓を用いた超音波血栓溶解療法における最小有効音響強度の検証

摘要

Human herpesvirus 6 (HHV-6) is a nononcogenic lymphotropic beta herpesvirus. HHV-6 can be classified into 2 variants: HHV-6 variant A and HHV-6 variant B (HHV-6B). Like other herpesviruses, HHV-6 establishes a latent infection within monocytes and macrophages after primary infection. HHV-6 has been shown to specifically integrate into the telomeres of chromosomes (chromosomally integrated HHV-6, CIHHV-6) in approximately 1% of the human population and to be vertically transmitted through the germ-line. Despite the consistent and frequent detection of CIHHV-6, it remains unclear how HHV-6 genomic DNA integrates into the human genome and whether persons with CIHHV-6 are at clinical risk. Here, we describe our establishment of the 293T cell line carrying integrated HHV-6B (293TintH6B) using a novel recombinant HHV-6B (H6BR28LEP) and 293T cells to determine the mechanism involved in the HHV-6 integration. A Basic Local Alignment Search Tool homology search of 293TintH6B genomic DNA confirmed the presence of an HHV-6B DNA right direct repeat telomeric sequence joined with TAACCC telomere repeats and of a chromosome 4q35 subtelomere sequence. Quantitative real-time polymerase chain reaction analysis revealed that 1 complete copy HHV-6B genomic DNA was included in each cell. Although the immediate early gene (U90) and the early gene (U25, U42) mRNA expression were detected at the beginning of 293TintH6B cell establishment, the expression of each mRNA was gradually silenced during the proliferation of 293TintH6B cells. These observations suggest that 293TintH6B cells represent the initial event of HHV-6B integration to all somatic cells, including germ cells, and that HHV-6B is maintaining the stable latent infection by integrating its genome into a telomeric region under a telomere-specific gene-silencing mechanism.%現在，脳血管疾患は本邦死因の第4位を占め，その6割近くが脳梗塞とされている.その超急性期治療法として，わが国でも，血栓溶解剤である組み換え組織プラスミノーゲン活性化因子（rt-PA：recombinant tissue-Plasminogen activator）　による経静脈的血栓溶解療法の有効性が証明され，平成17年から保険診療が可能となっている.