Deitz S B, Dodd D A, Cooper S, Parham P, Kirkegaard K
Departments of Microbiology and Immunology, and Structural Biology, Stanford University, School of Medicine, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13790-5. doi: 10.1073/pnas.250483097.
The effects of poliovirus 3A protein expression and poliovirus infection on the presentation of hepatitis C virus antigens in cultured chimpanzee cells were examined. Expression of poliovirus 3A protein inhibits protein secretion when expressed in isolation and was sufficient to protect chimpanzee cells from lysis by hepatitis C virus-specific cytotoxic T cells in standard (51)Cr-release assays. Poliovirus infection also inhibited antigen presentation, as determined by decreased cytotoxic T cell activation. A mutation in 3A that abrogates the inhibition of protein secretion also abolished the effects of poliovirus on antigen presentation. These results demonstrate that the inhibition of secretion observed in poliovirus-infected cells substantially reduces the presentation of new antigens on the cell surface. These observations may reflect a general mechanism by which nonenveloped viruses such as poliovirus and other viruses that do not require a functional protein secretory apparatus can evade detection by the cellular immune response.
研究了脊髓灰质炎病毒3A蛋白表达及脊髓灰质炎病毒感染对培养的黑猩猩细胞中丙型肝炎病毒抗原呈递的影响。脊髓灰质炎病毒3A蛋白单独表达时可抑制蛋白质分泌,并且在标准的(51)铬释放试验中足以保护黑猩猩细胞免受丙型肝炎病毒特异性细胞毒性T细胞的裂解。如通过细胞毒性T细胞活化降低所确定的,脊髓灰质炎病毒感染也抑制抗原呈递。3A中的一个消除蛋白质分泌抑制作用的突变也消除了脊髓灰质炎病毒对抗原呈递的影响。这些结果表明,在脊髓灰质炎病毒感染的细胞中观察到的分泌抑制作用显著降低了细胞表面新抗原的呈递。这些观察结果可能反映了一种普遍机制,通过该机制,诸如脊髓灰质炎病毒等无包膜病毒以及其他不需要功能性蛋白质分泌装置的病毒可以逃避细胞免疫反应的检测。