Virus-encoded ectopic CD74 enhances poxvirus vaccine efficacy.
Virus-encoded ectopic CD74 enhances poxvirus vaccine efficacy.
复制标题
病毒编码的异位 CD74 增强了痘病毒疫苗的功效。
DOI：
10.1111/imm.12210
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发表时间：
2014
期刊：
影响因子：
6.4
通讯作者：
Blum,JaniceS
中科院分区：
文献类型：
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作者：
Walline,CrystalC;Deffit,SarahN;Wang,Nan;Guindon,LynetteM;Crotzer,VictoriaL;Liu,Jianyun;Hollister,Kristin;Eisenlohr,LaurenceC;Brutkiewicz,RandyR;Kaplan,MarkH;Blum,JaniceS
痘苗病毒(VV)已在全球范围内被用作根除天花的疫苗。这种病毒疫苗的广泛使用近年来得到了缓和，因为它具有免疫规避特性，限制了免疫缺陷或特应性皮肤病患者接种VV疫苗。已知VV感染扰乱了多种免疫识别途径，包括MHC II类(MHCII)和CD1d限制性抗原提呈。MHCII和CD1d分子与保守的细胞内伴侣CD74相关，CD74也称为不变链。在VV感染后，抗原提呈细胞中的CD74水平显著降低，这与观察到的MHCII分子的不稳定一致。在目前的研究中，研究了持续表达CD74以克服VV诱导的抗原提呈抑制的能力。CD74的异位表达或用编码小鼠CD74的重组VV(mCD74-VV)感染细胞可部分改善病毒对MHCII抗原提呈的抑制作用。相反，病毒诱导的CD1d介导的抗原提呈中断即使在CD74持续表达的情况下也持续存在。重组mCD74-VV免疫小鼠在VV攻击中表现出更强的保护力和更强的抗VV抗体反应。综上所述，这些观察结果表明，编码CD74的重组VV疫苗可能是提高CD4+T细胞对病毒和肿瘤抗原反应的有用工具。
Vaccinia virus (VV) has been used globally as a vaccine to eradicate smallpox. Widespread use of this viral vaccine has been tempered in recent years because of its immuno‐evasive properties, with restrictions prohibiting VV inoculation of individuals with immune deficiencies or atopic skin diseases. VV infection is known to perturb several pathways for immune recognition including MHC class II (MHCII) and CD1d‐restricted antigen presentation. MHCII and CD1d molecules associate with a conserved intracellular chaperone, CD74, also known as invariant chain. Upon VV infection, cellular CD74 levels are significantly reduced in antigen‐presenting cells, consistent with the observed destabilization of MHCII molecules. In the current study, the ability of sustained CD74 expression to overcome VV‐induced suppression of antigen presentation was investigated. Viral inhibition of MHCII antigen presentation could be partially ameliorated by ectopic expression of CD74 or by infection of cells with a recombinant VV encoding murine CD74 (mCD74‐VV). In contrast, virus‐induced disruptions in CD1d‐mediated antigen presentation persisted even with sustained CD74 expression. Mice immunized with the recombinant mCD74‐VV displayed greater protection during VV challenge and more robust anti‐VV antibody responses. Together, these observations suggest that recombinant VV vaccines encoding CD74 may be useful tools to improve CD4+T‐cell responses to viral and tumour antigens.