Evasion of Cytotoxic T Lymphocyte (CTL) Responses by Nef-dependent Induction of Fas Ligand (CD95L) Expression on Simian Immunodeficiency Virus–infected Cells
Evasion of Cytotoxic T Lymphocyte (CTL) Responses by Nef-dependent Induction of Fas Ligand (CD95L) Expression on Simian Immunodeficiency Virus–infected Cells
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通过 Nef 依赖性诱导 Fas 配体 (CD95L) 在猿免疫缺陷病毒感染细胞上表达来逃避细胞毒性 T 淋巴细胞 (CTL) 反应
DOI：
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发表时间：
1997
影响因子：
15.3
通讯作者：
A. McMichael
中科院分区：
文献类型：
--
作者：
Xiao;G. Screaton;F. Gotch;T. Dong;R. Tan;N. Almond;B. Walker;R. Stebbings;K. Kent;S. Nagata;J. Stott;A. McMichael
用减毒SIV活毒株接种猕猴已被证明可保护其免受随后的野生型SIV攻击。保护机制仍然模糊不清。为了更详细地研究这种效应，我们研究了与野生型SIVmac 32 H克隆（pJ 5）相比，在感染减毒SIV株（pC 8）的猕猴中病毒特异性CTL应答的作用，该减毒SIV株在nef基因中具有4个氨基酸缺失。用pC 8感染的食蟹猴被保护免于随后用pJ 5的攻击，并且在感染后12个月内没有出现任何AIDS样症状。pC 8诱导的保护作用与对多种病毒抗原的高水平病毒特异性CTL应答相关。相比之下，pJ 5感染的猕猴在三个月后对病毒蛋白几乎没有可检测到的CTL应答。后一组猕猴也表现出增加的Fas表达和凋亡细胞死亡的CD 4+和CD 8+群体。在体外，pJ 5而不是pC 8导致感染细胞上FasL表达的增加。因此，FasL的表达可以保护感染的细胞免受CTL攻击，在此过程中杀死病毒特异性CTL，并提供逃避免疫应答的途径，导致pJ 5的致病性增加。另一方面，pC 8不诱导FasL表达，允许保护性CTL应答的发展。此外，Fas-FasL相互作用的中断允许在pJ 5感染的动物中再生病毒特异性CTL应答。这一观察结果表明了治疗艾滋病的另一种治疗方法。
Inoculation of macaques with live attenuated SIV strains has been shown to protect against subsequent challenge with wild-type SIV. The protective mechanism(s) remain obscure. To study the effect in more detail, we have investigated the role of virus-specific CTL responses in macaques infected with an attenuated SIV strain (pC8), which has a four–amino acid deletion in the nef gene, as compared with the wild-type SIVmac32H clone (pJ5). Cynomolgus macaques infected with pC8 were protected against subsequent challenge with pJ5 and did not develop any AIDS-like symptoms in the 12 months after infection. The pC8-induced protection was associated with high levels of virus-specific CTL responses to a variety of viral antigens. In contrast, pJ5-infected macaques had little, if any, detectable CTL response to the viral proteins after three months. The latter group of macaques also showed increased Fas expression and apoptotic cell death in both the CD4+ and CD8+ populations. In vitro, pJ5 but not pC8 leads to an increase in FasL expression on infected cells. Thus the expression of FasL may protect infected cells from CTL attack, killing viral-specific CTLs in the process, and providing a route for escaping the immune response, leading to the increased pathogenicity of pJ5. pC8, on the other hand does not induce FasL expression, allowing the development of a protective CTL response. Furthermore, interruption of the Fas-FasL interaction allows the regeneration of viral-specific CTL responses in pJ5-infected animals. This observation suggests an additional therapeutic approach to the treatment of AIDS.
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被猿猴免疫缺陷病毒 SIV/Mne 感染的 CD4 人淋巴细胞系中的病毒和细胞基因表达。
影响因子：
3.7
作者：
Agy,MB;Foy,K;Gale,MJ;Benveniste,RE;Clark,EA;Katze,MG
通讯作者：
Katze,MG
DOI：
10.1073/pnas.92.16.7312
发表时间：
1995-08
影响因子：
11.1
作者：
B. Nardelli;C. Gonzalez;M. Schechter;F. Valentine
通讯作者：
B. Nardelli;C. Gonzalez;M. Schechter;F. Valentine
影响因子：
15.9
作者：
ROEDERER, M;DUBS, JG;HERZENBERG, LA
通讯作者：
HERZENBERG, LA
影响因子：
4.4
作者：
Dorothy E. Lewis;D. N. Tang;A. Adu-Oppong;Wendy Schober;J. Rodgers
通讯作者：
Dorothy E. Lewis;D. N. Tang;A. Adu-Oppong;Wendy Schober;J. Rodgers
男同性恋者感染 HIV 1 型前 8 年的抗 HIV 1 型细胞毒性 T 淋巴细胞效应活性和疾病进展。
影响因子：
1.5
作者：
RinaldoJr,CR;Beltz,LA;Huang,XL;Gupta,P;Fan,Z;Torpey3rd,DJ
通讯作者：
Torpey3rd,DJ