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）是对这些疱疹病毒感染的SIS的新人类疱疹病毒从现在的礼物中如下：1。N当HV-6插入的细胞在TNF-A和抗FAS抗体的存在下培养时凋亡程度增加。 .2。具有……更多HHV-7.3的结合受体。 6B的重新激活HV-6。 CCR5在HHV-7感染的细胞中被检测到CXCR4的离子，导致趋化性障碍，并降低了对SDF-1的细胞内Ca^<2+反应的升高。 HV-7感染的CD4^+T细胞表现出明显降低的CXCR4基因转录水平，但CXCR4 mRNA的转录后稳定性并未显着改变

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。

Tohyama,M.,et al: "Severe hypersensitivity syndrome to sulfasalazine associated with reactivvation of human herpesvirus 6" Archives of Dermatology. 134. 1113-1117 (1998)

Tohyama，M.，等人：“与人类疱疹病毒 6 重新激活相关的柳氮磺吡啶严重过敏综合征”皮肤病学档案。

Masaki Yasukawa, et al.: "Apoptosis of CD4+ T lymphocytes in human herpesvirus-6 infection" Journal of General Virology. 79. 143-147 (1998)

Masaki Yasukawa 等人：“人类疱疹病毒 6 感染中 CD4 T 淋巴细胞的凋亡”普通病毒学杂志。