Therapeutic Potential of IL-15 and N-803 in HIV/SIV Infection.
Therapeutic Potential of IL-15 and N-803 in HIV/SIV Infection.
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DOI：
10.3390/v13091750
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发表时间：
2021-09-02
期刊：
影响因子：
--
通讯作者：
O'Connor S
中科院分区：
文献类型：
--
作者：
Harwood O;O'Connor S
IL-15是一种对T细胞应答的产生、维持和稳态至关重要的促炎细胞因子，其在响应HIV/SIV感染时自然产生，但也已显示出治疗潜力。IL-15可以促进CD 4+和CD 8 + T细胞和NK细胞的增殖、活化和功能。然而，在某些情况下，IL-15治疗可能导致异常免疫激活和加速疾病进展。此外，IL-15给药时机与疾病进展之间的关系仍不清楚。开发IL-15超激动剂N-803是为了通过最大化其组织分布和半衰期来扩大IL-15的治疗潜力。最近，N-803作为一种增强对HIV/SIV的先天性和细胞免疫应答的方法，通过改善CD 8 + T细胞识别和杀死病毒感染的细胞，并将免疫细胞引导到粘膜部位和淋巴结（病毒复制的主要部位），引起了人们的热情。由于N-803具有逆转潜伏期（休克）和增强抗病毒免疫（杀死）的潜力，因此也在“休克和杀死”策略中进行了评价。本文综述了目前关于IL-15和N-803对先天免疫和细胞免疫、病毒负荷和HIV/SIV背景下潜伏期逆转的影响的文献，以及它们单独和与抗逆转录病毒治疗（ART）和疫苗接种等其他干预措施相结合的治疗潜力。
IL-15, a proinflammatory cytokine critical for the generation, maintenance, and homeostasis of T cell responses, is produced naturally in response to HIV/SIV infection, but has also demonstrated therapeutic potential. IL-15 can boost CD4+ and CD8+ T cell and NK cell proliferation, activation, and function. However, IL-15 treatment may cause aberrant immune activation and accelerated disease progression in certain circumstances. Moreover, the relationship between the timing of IL-15 administration and disease progression remains unclear. The IL-15 superagonist N-803 was developed to expand the therapeutic potential of IL-15 by maximizing its tissue distribution and half-life. N-803 has garnered enthusiasm recently as a way to enhance the innate and cellular immune responses to HIV/SIV by improving CD8+ T cell recognition and killing of virus-infected cells and directing immune cells to mucosal sites and lymph nodes, the primary sites of virus replication. N-803 has also been evaluated in “shock and kill” strategies due to its potential to reverse latency (shock) and enhance antiviral immunity (kill). This review examines the current literature about the effects of IL-15 and N-803 on innate and cellular immunity, viral burden, and latency reversal in the context of HIV/SIV, and their therapeutic potential both alone and combined with additional interventions such as antiretroviral therapy (ART) and vaccination.
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影响因子：
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DOI：
10.1016/s2352-3018(15)00226-x
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2015-12
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The lancet. HIV
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