The CD8⁺ T cell noncytotoxic antiviral response (CNAR) was discovered during studies of asymptomatic HIV-infected subjects more than 30 years ago. In contrast to CD8⁺ T cell cytotoxic lymphocyte (CTL) activity, CNAR suppresses HIV replication without target cell killing. This activity has characteristics of innate immunity: it acts on all retroviruses and thus is neither epitope specific nor HLA restricted. The HIV-associated CNAR does not affect other virus families. It is mediated, at least in part, by a CD8⁺ T cell antiviral factor (CAF) that blocks HIV transcription. A variety of assays used to measure CNAR/CAF and the effects on other retrovirus infections are described. Notably, CD8⁺ T cell noncytotoxic antiviral responses have now been observed with other virus families but are mediated by different cytokines. Characterizing the protein structure of CAF has been challenging despite many biologic, immunologic, and molecular studies. It represents a low-abundance protein that may be identified by future next-generation sequencing approaches. Since CNAR/CAF is a natural noncytotoxic activity, it could provide promising strategies for HIV/AIDS therapy, cure, and prevention.

中文翻译：

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CD8+ T 细胞非细胞毒性抗病毒反应


CD8 ⁺ T 细胞非细胞毒性抗病毒反应 (CNAR) 是 30 多年前在对无症状 HIV 感染者的研究中发现的。与 CD8 ⁺ T 细胞细胞毒性淋巴细胞 (CTL) 活性相反，CNAR 可以抑制 HIV 复制而不杀死靶细胞。这种活性具有先天免疫的特征：它作用于所有逆转录病毒，因此既不是表位特异性的，也不是 HLA 限制的。与 HIV 相关的 CNAR 不会影响其他病毒家族。它至少部分是由阻止 HIV 转录的 CD8 ⁺ T 细胞抗病毒因子 (CAF) 介导的。描述了用于测量 CNAR/CAF 的多种测定法以及对其他逆转录病毒感染的影响。值得注意的是，现已在其他病毒家族中观察到 CD8 ⁺ T 细胞非细胞毒性抗病毒反应，但由不同的细胞因子介导。尽管进行了许多生物学、免疫学和分子学研究，但表征 CAF 的蛋白质结构仍然具有挑战性。它代表了一种低丰度蛋白质，可以通过未来的下一代测序方法来识别。由于 CNAR/CAF 是一种天然的非细胞毒性活性，因此它可以为 HIV/AIDS 的治疗、治愈和预防提供有前景的策略。