Molecular analysis of new herpesvirusinfections

新疱疹病毒感染的分子分析

• 批准号: 09670477
• 负责人: YASUKAWA Masaki
• 金额: $ 1.92万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670477/
• 关键词: Herpesviruses; HHV-6; HHV-7; KSHV; HHV-8; Apoptosis; CD4; CXCR4

Human herpesvirus 6 (HHV-6), HHV-7 and KSHV (HHV-8) are new human herpesviruses which have been recently isolated. In the present study, the pathogenesis of these herpesvirus infections was investigated focusing on the functional alteration of virus-infected CD4+T lymphocytes. Results obtained from the series of the present study are as follows :1. HHV-6 infection of CD4+T lymphocytes resulted in their apoptosis. The degree of apoptosis increased when HHV-6-inoculated cells were cultured in the presence of TNF-a and anti-Fas antibody. HHV-6 induces apoptosis in CD4^+T cells by indirect mechanisms, as reported recently in HIV-1 infection.2. We examined the susceptibility to HHV-7 infection of various CD4-negative cell lines into which the cDNA for CD4 was transferred using an adenovirus vector. Out of 13 cell lines transduced with Adex1CACD4, 4 cell lines showed high susceptibility to HHV-7 infection. These data suggest strongly that CD4 is a major component of the binding receptor for … More HHV-7.3. Two novel Ph chromosome-positive myeloid cell lines, SAS4l3 and SAS527, which possess different hematologic characteristics and show distinct susceptibility to infection of HHV-6, have been established. TPA-treatment of SAS527 which was latently infected with HHV-6B resulted in reactivation of HHV-6. These novel cell lines should be useful for studying the mechanisms of HHV-6- induced hematopoietic failure and HHV-6 latency and reactivation.4. Although CXCR4 and CCR5 appeared not to be the coreceptors for these viruses, marked down-regulation of CXCR4, but not CCR5, was detected in HHV-6 and HHV-7-infected cells. Down-regulation of CXCR4 resulted in impairment of chemotaxis and a decreased level of elevation of the intracellular Ca^<2+> concentration in response to SDF-1. Northern blot analysis of mRNAs extracted from HHV-6- and HHV-7-infected CD4^+T lymphocytes demonstrated a markedly decreased level of CXCR4 gene transcription, but post-transcriptional stability of CXCR4 mRNA was not significantly altered. Less

人类疱疹病毒 6 (HHV-6)、HHV-7 和 KSHV (HHV-8) 是最近分离的新人类疱疹病毒。在本研究中，研究了这些疱疹病毒感染的发病机制，重点是病毒感染的 CD4+T 淋巴细胞的功能改变。本研究系列获得的结果如下： 1． HHV-6感染CD4+T淋巴细胞导致其凋亡。当HHV-6接种的细胞在TNF-α和抗Fas抗体存在下培养时，细胞凋亡程度增加。正如最近在HIV-1感染中报道的那样，HHV-6通过间接机制诱导CD4^+T细胞凋亡。2．我们检查了使用腺病毒载体将 CD4 的 cDNA 转移到其中的各种 CD4 阴性细胞系对 HHV-7 感染的敏感性。在用 Adex1CACD4 转导的 13 个细胞系中，有 4 个细胞系表现出对 HHV-7 感染的高敏感性。这些数据强烈表明 CD4 是 HHV-7.3 结合受体的主要成分。已建立了两种新型 Ph 染色体阳性骨髓细胞系 SAS4l3 和 SAS527，它们具有不同的血液学特征，并对 HHV-6 感染表现出不同的易感性。对潜伏感染 HHV-6B 的 SAS527 进行 TPA 处理导致 HHV-6 重新激活。这些新的细胞系对于研究HHV-6诱导的造血衰竭以及HHV-6潜伏和再激活的机制应该有用。4．尽管 CXCR4 和 CCR5 似乎不是这些病毒的辅助受体，但在 HHV-6 和 HHV-7 感染的细胞中检测到 CXCR4 显着下调，而非 CCR5。 CXCR4的下调导致趋化性受损以及响应于SDF-1的细胞内Ca 2+ 浓度升高水平降低。从 HHV-6 和 HHV-7 感染的 CD4^+T 淋巴细胞中提取的 mRNA 的 Northern 印迹分析表明 CXCR4 基因转录水平显着降低，但 CXCR4 mRNA 的转录后稳定性没有显着改变。较少的

项目成果

Yasukawa, M., et al.: "Down-regulation of CXCR4 by human herpesvirus 6 (HHV-6) and HHV-7" Journal of Immunology. (in press.).

Yasukawa, M., et al.：“人疱疹病毒 6 (HHV-6) 和 HHV-7 下调 CXCR4”免疫学杂志。

Yasukawa,M.,et al.: "Human herpesvirus 7 infection of lymphoid and myeloid cell lines transduced with an adenovirus vector ・・・・・" Journal of Virology. 71. 1708-1712 (1997)

Yasukawa, M., et al.：“用腺病毒载体转导的人疱疹病毒 7 感染淋巴和骨髓细胞系……”病毒学杂志 71. 1708-1712 (1997)。

Inoue, Y., et al.: "Induction of T-cell apoptosis by human herpesvirus 6" Journal of Virology. 71. 3751-3759 (1997)

Inoue, Y., et al.：“人类疱疹病毒 6 诱导 T 细胞凋亡”病毒学杂志。

Inoue,Y.,et al.: "Induction of T-cell apoptosis by human herpesvirus 6" Journal of Virology. 71. 3751-3759 (1997)

Inoue,Y.,et al.：“人类疱疹病毒 6 诱导 T 细胞凋亡”病毒学杂志。

Yasukawa, M.et al.: "Human herpesvirus 7 infection of lymphoid and myeloid cell lines transduced with an adenovirus vector containing the CD4 gene" Journal of Virology. 71. 1708-1712 (1997)

Yasukawa, M.等人：“用含有 CD4 基因的腺病毒载体转导的淋巴和骨髓细胞系的人疱疹病毒 7 感染”病毒学杂志。