Nature medicine：治疗慢性病毒感染有新招

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       近日，来自美国的科学家在著名国际期刊nature medicine在线发表了他们的最新研究进展，他们发现慢性病毒感染如HIV等会导致细胞毒性T淋巴细胞功能衰退，在这个过程中前列腺素E2（PGE2）相关信号通路发挥了重要促进作用，因此，抑制PEG2或是治疗慢性病毒感染的一种有效手段。

       目前，世界上有超过10%的人口正遭受HIV,HCV和HBV等慢性病毒感染的折磨，这几种疾病均可能引发严重并发症甚至死亡。持续的抗原刺激会引起病毒特异性的细胞毒性T淋巴细胞（CTL）发生功能衰退，细胞死亡，导致HIV,HCV和HBV等病毒持续存在。除此之外，抗病毒性CTL会通过上调抑制性受体，如PD-1，自发性抑制它们对免疫病原体的限制作用。发现并阻断这些诱导CTL紊乱的信号途径可能有助于清除慢性病毒感染。

       研究人员发现在慢性淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染过程中前列腺素E2（PGE2）受体EP2和EP4在病毒特异性CTL中会发生上调，抑制CTL存活和正常功能发挥。他们证明联合阻断PGE2和PD-1信号途径在改善病毒控制，扩增具有正常功能的病毒特异性CTL细胞方面具有很好的效果。

       综上所述，该项研究证明抑制PEG2既是一种靶向治疗慢性病毒感染的独立治疗手段，又能够与阻断PD-1信号联合作用治疗慢性病毒感染，具有重要应用前景。

[size=16.3636360168457px]http://news.bioon.com/article/6667339.html

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Prostaglandin E2 and programmed cell death 1 signaling coordinately impair CTL function and survival during chronic viral infection

Jonathan H Chen,Curtis J Perry,Yao-Chen Tsui,Matthew M Staron,Ian A Parish,Claudia X Dominguez,Daniel W Rosenberg& Susan M Kaech

More than 10% of the world's population is chronically infected with HIV, hepatitis C virus (HCV) or hepatitis B virus (HBV), all of which can cause severe disease and death. These viruses persist in part because continuous antigenic stimulation causes the deterioration of virus-specific cytotoxic T lymphocyte (CTL) function and survival. Additionally, antiviral CTLs autonomously suppress their responses to limit immunopathology by upregulating inhibitory receptors such as programmed cell death 1 (PD-1). Identification and blockade of the pathways that induce CTL dysfunction may facilitate the clearance of chronic viral infections. We found that the prostaglandin E2 (PGE2) receptors EP2 and EP4 were upregulated on virus-specific CTLs during chronic lymphocytic choriomeningitis virus (LCMV) infection and suppressed CTL survival and function. We show that the combined blockade of PGE2 and PD-1 signaling was therapeutic in terms of improving viral control and augmenting the numbers of functional virus-specific CTLs. Thus, PGE2 inhibition is both an independent candidate therapeutic target and a promising adjunct therapy to PD-1 blockade for the treatment of HIV and other chronic viral infections.

[size=16.3636360168457px]http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3831.html