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型（HHV-6）、7型（HHV-7）和8型（KSHV-8）是近年来分离到的新的人类疱疹病毒。在本研究中，这些疱疹病毒感染的发病机制进行了研究，重点是病毒感染的CD 4 +T淋巴细胞的功能改变。本研究的主要结果如下：1. HHV-6感染CD 4 +T淋巴细胞可导致其凋亡。在TNF-α和抗Fas抗体存在下，接种HHV-6的细胞凋亡程度增加。HHV-6通过间接机制诱导CD 4 ^+T细胞凋亡，如最近在HIV-1感染中报道的。我们研究了各种CD 4阴性细胞系对HHV-7感染的易感性，其中使用腺病毒载体将CD 4的cDNA转移到这些细胞系中。Adex 1CACD 4转导的13株细胞中，有4株细胞对HHV-7感染表现出高度易感性。这些数据有力地表明，CD 4是结合受体的主要成分， ...更多信息 HHV-7.3建立了两种新的Ph染色体阳性髓系细胞系，SAS 413和SAS 527，它们具有不同的血液学特性，并显示出对HHV-6感染的明显易感性。TPA处理潜伏感染HHV-6 B的SAS 527导致HHV-6再活化。这些新的细胞系将有助于研究HHV-6诱导造血功能衰竭的机制以及HHV-6潜伏和再激活的机制.虽然CXCR 4和CCR 5似乎不是这些病毒的共受体，但在HHV-6和HHV-7感染的细胞中检测到CXCR 4的显著下调，而不是CCR 5。CXCR 4的下调导致趋化性受损，并降低了SDF-1引起的细胞内Ca^2+浓度升高水平。从HHV-6和HHV-7感染的CD 4 ^+T淋巴细胞中提取mRNA，进行北方印迹分析，结果显示CXCR 4基因转录水平显著降低，但CXCR 4 mRNA转录后稳定性没有显著改变。少

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。