| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
We have studied the latent and the productive infection of HHV-6 in the peripheral blood macrophages. As for the study on HHV-6 latency, four kinds of latency-associated transcripts of human herpesvirus 6 were identified, which were detected only in latently infected cells. Although they were encoded in the same direction as the immediate early (IE) 1/2 genes and shared their protein-coding region with IE1/2, their transcription start sites and exon(s) were latency-associated. Our findings revealed that the structures, the encoded proteins, and the expression of the HHV-6 latency-associated transcripts were similar to those of HCMV latency-specific transcripts. The H6LTs and the HCMV latency-specific transcripts may have some common function during latency. The conserved features of the HHV-6 and HCMV latent transcripts that we observed in this study may assist us in understanding β-herpesvirus latency further. As for the study on the acute infection, we investigated the tropism of HHV-6 in peripheral blood mononuclear cells (PBMCs) during acute infection. We detected 637 ± 273 copies of viral DNA in 10^4 MO/Mφ. In contrast, in 10^4CD4^+T cells, which have been reported to be viral carriers during the acute infection of HHV-6, we found only 115 ± 42 copies of viral DNA. Consistent with these data, virus was isolated from MO/Mφ an order of magnitude more frequently than from CD4^+ T cells. Viral mRNA U79/80, which indicates viral replication, was detectable in the MO/Mφ. In addition, the mRNAs that encode viral chemokine receptors U12 and U51, which may modify the function of MO/Mφ, were expressed in the cells. Therefore, productively infected MO/Mφ may be the dominant cell population that is responsible for HHV-6 viremia during acute HHV-6 infection. The strong interaction of HHV-6 with MO/Mφ may be partly responsible for the pathogenesis of this virus.
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