权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Escape mechanisms of HIV-1 from HIV-1-specific CTLs

HIV-1 从 HIV-1 特异性 CTL 中逃逸的机制

基本信息

批准号：
18390141
负责人：
TAKIGUCHI Masafumi
金额：
$ 10.44万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390141/
关键词：
Virus Pathogenesis Control of infection HIV-1 T Cell

项目摘要

It is well known that HLA-B^*57/58, -B^*27, and -B*^51 alleles are associated with slow disease progression to AIDS, but the role of cytotoxic T lymphocytes(CTLs)restricted by these alleles in long-term control of HIV-1 still remains unknown. We investigated HIV-1-specific CTLs in long-term non-progressing(LTNP)and slow-progressing(slow progressors)hemophiliacs carrying HLA-B^*5101. Both Pol283-8-specific and Pol743-9-specific CTLs, which have a strong ability to suppress HIV-1 replication in vitro, were detected in LTNPs whereas only Pol743-9-specific CTLs were found in the slow progressors. The LTNPs had HIV-1 possessing wild-type sequence in these epitopes or a mutation reducing the ability of the specific CTLs to suppress HIV-1 replication and viral fitness. In contrast, the slow progressors and progressors had HIV-1 with escape mutations that did not influence viral fitness. Longitudinal analysis of a hemophiliac confirmed the association between the appearance of a Pol283-8 escape mutant and a high viral load. The induction of HIV-1-specific CTLs with a strong ability to suppress HIV-1 replication and the evolution to a mutant with reduced viral fitness and T cell recognition were found to be necessary for the control of HIV-1 for approximately 25 years.

众所周知，HLA-B^*57/58、-B^*27和-B*^51等位基因与艾滋病的缓慢疾病进展相关，但受这些等位基因限制的细胞毒性T淋巴细胞（CTL）在长期控制HIV-1中的作用仍不清楚。我们研究了携带HLA-B^*5101的长期非进展（LTNP）和缓慢进展（缓慢进展者）血友病患者中的HIV-1特异性CTL。在LTNP中检测到Pol 283 -8特异性和Pol 743 -9特异性CTL，它们具有很强的体外抑制HIV-1复制的能力，而在缓慢进展者中仅发现Pol 743 -9特异性CTL。LTNP具有在这些表位中具有野生型序列的HIV-1或降低特异性CTL抑制HIV-1复制和病毒适应性的能力的突变。相比之下，缓慢进展者和进展者的HIV-1逃逸突变不影响病毒适应性。对血友病患者的纵向分析证实了Pol 283 -8逃逸突变体的出现与高病毒载量之间的关联。诱导HIV-1特异性CTL具有很强的抑制HIV-1复制的能力，并进化为病毒适应性和T细胞识别能力降低的突变体，被发现是控制HIV-1大约25年所必需的。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Different Ability of Escape Mutant-Specific Cytotoxic T Cells to Suppress Replication of Escape Mutant and Wild-type HIV-1 in New Hosts

逃逸突变体特异性细胞毒性 T 细胞抑制逃逸突变体和野生型 HIV-1 在新宿主中复制的不同能力

DOI：
发表时间：
2008
期刊：
Journal of Virology 82
影响因子：
0
作者：
Nogi T;Yasui N;Mihara E;Matsunaga Y;Noda M;Yamashita N;Toyofuku T;Uchiyama S;Goshima Y;Kumanogoh A;Takagi J.;Mamoru Fujiwara
通讯作者：
Mamoru Fujiwara

Involvement of multiple epitope-specific cytotoxic T-lymphocyte responses in vaccine-based control of simian immunodeficiency virus replication in rhesus macaques