Functional adaptation of HIV accessory proteins towardimmune-mediated selective pressure

HIV辅助蛋白对免疫介导的选择压力的功能适应

• 批准号: 22390089
• 负责人: UENO Takamasa
• 金额: $ 11.9万
• 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: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390089/
• 关键词: 感染防御; ワクチン; ウイルス; 感染症; 免疫学; 進化

Impaired HIV-1 Gag, Pol, and Env function has been described inelite controllers (EC) who spontaneously suppress plasma viremia to < 50 RNA copies/mL;however, activity of the accessory protein Nef remains incompletely characterized. Weexamined the ability of 91 Nef sequences, isolated from plasma of 45 EC and 46 chronicprogressors (CP), to down-regulate HLA class I and CD4, up-regulate HLA class II invariantchain (CD74), enhance viral infectivity, and stimulate viral replication in PBMC. Ingeneral, EC Nef sequences were functional; however, all five activities weresignificantly lower in EC compared to CP. Nef from HLA-B*57-expressing EC exhibited poorerCD4 down-regulation function compared to non-B*57 EC, and the number of EC-specificB*57-associated Nef polymorphisms correlated inversely with 4 of 5 Nef functions in theseindividuals. Results indicate that decreased viral protein function, due in part to hostimmune selection pressures, may be a hallmark of the EC phenotype.

HIV-1 Gag、Pol和Env功能受损已在自发将血浆病毒血症抑制到50RNA拷贝/毫升的精英控制者(EC)中描述；然而，辅助蛋白Nef的活性仍未完全确定。我们检测了从45例EC和46例慢性进展者(CP)血浆中分离到的91个Nef序列下调人类白细胞抗原I类和CD4，上调人类白细胞抗原II类不变链(CD74)，增强病毒感染性，并刺激病毒在PBMC中复制的能力。总体而言，EC的Nef序列是功能性的；然而，EC的所有五种活性都显著低于CP。与非B*57表达的EC相比，表达HLA-B*57的EC的Nef表现出更差的CD4下调功能，并且EC特有的B*57相关Nef多态的数目与这些个体中5种Nef功能中的4种呈负相关。结果表明，病毒蛋白功能降低，部分原因是主机免疫选择压力，可能是EC表型的一个特征。

项目成果

Genetic and functional analysesof HIV-1 Nef in elite controllers

精英控制者中 HIV-1 Nef 的遗传和功能分析

• 发表时间: 2012
• 作者: 上 野 貴 将 ; Mwimanzi Philip ; MarkleTristan;緒方陽子; 徳永美知代;MahitiMacdonald; 三浦聡之; Pereyra Florencia;Walker Bruce; Brumme Zabrina; BrockmanMark
• 通讯作者: BrockmanMark

HIV-1 immune escape andcross-reactivity profiles ofvirus-specific cytotoxic Tlymphocytes, YIS-A Session II

HIV-1 免疫逃逸和病毒特异性细胞毒性 T 淋巴细胞的交叉反应特征，YIS-A 第二部分

• 发表时间: 2012
• 作者: Chihiro Motozono;John J. Miles,Zafrul Hasan;Hiroyuki Gatanaga,Meribe Stanley;Shinichi Oka;MasaakiMiyazawa;Andrew K. Sewell;TakamasaUeno
• 通讯作者: TakamasaUeno

Modulation of HIV-1Nef-mediated HLA class Idown-regulation activity duringdisease progression

疾病进展过程中 HIV-1Nef 介导的 HLA I 类下调活性的调节

• 发表时间: 2012
• 作者: M. Mahiti;P. Mwimanzi;Y. Ogata;M.Tokunaga;B. Walker;Z. Brumme;M.Brockman;T. Ueno
• 通讯作者: T. Ueno

Naturally arising HIV-1 Nef variants conferring escape from cytotoxic T lymphocytes influence viral entry co-receptor expression and susceptibility to superinfection.

• DOI: 10.1016/j.bbrc.2010.11.047
• 发表时间: 2010-12
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: P. Mwimanzi;Zafrul Hasan;Michiyo Tokunaga;H. Gatanaga;S. Oka;T. Ueno

HLA class I-mediatedsequence polymorphism in HIV-1accessory protein Vpu

HIV-1辅助蛋白Vpu中HLA I类介导的序列多态性

• 发表时间: 2012
• 作者: Zafrul Hasan;J. Carlson;H. Gatanaga,A. Le;C. Brumme;S. Oka;Z. Brumme,Takamasa Ueno
• 通讯作者: Z. Brumme,Takamasa Ueno