研究人员发现一种新蛋白能够阻止丙肝病毒的复制，这一发现将可能为丙肝新药的设计提供重要线索。
丙肝是一种血液携带的传染疾病，能够导致肝炎、肝硬化和肝癌。这种病毒通过复制自己的RNA在寄住体内传播，并利用RNA制造蛋白质、形成新病毒并抑制寄住细胞中不同的抗病毒蛋白质。
通过了解这两种机制，研究人员希望能够阻止病毒复制，进而终止感染。Stanley M. Lemon和同事发现一种新蛋白与终止这种病毒复制有个。这种蛋白质叫做p21活化激酶I，该蛋白在若干细胞信号途径中起到一定的作用，但之前并未证实与调节丙肝病毒的复制有关。
原始出处:
J. Biol. Chem., Vol. 282, Issue 16, 11836-11848, April 20, 2007
p21-activated Kinase 1 Is Activated through the Mammalian Target of Rapamycin/p70 S6 Kinase Pathway and Regulates the Replication of Hepatitis C Virus in Human Hepatoma Cells*
Hisashi Ishida, Kui Li, MinKyung Yi, and Stanley M. Lemon1
From the Center for Hepatitis Research, Institute for Human Infections and Immunity, and the Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1018
Cellular mechanisms that regulate the replication of hepatitis C virus (HCV) RNA are poorly understood. p21-activated kinase 1 (PAK1) is a serine/threonine kinase that has been suggested to participate in antiviral signaling. We studied its role in the cellular control of HCV replication. Transfection of PAK1-specific small interfering RNA enhanced viral RNA and protein abundance in established replicon cell lines as well as cells infected with chimeric genotype 1a/2a HCV, despite reducing cellular proliferation, suggesting specific regulation of HCV replication. PAK1 knockdown did not reduce interferon regulatory factor 3-dependent gene expression, indicating that this regulation is independent of the retinoic acid-inducible gene I/interferon regulatory factor 3 pathway. On the other hand, LY294002 and rapamycin abolished PAK1 phosphorylation and enhanced HCV abundance, suggesting that the mammalian target of rapamycin (mTOR) is involved in PAK1 regulation of HCV. Small interfering RNA knockdown of the mTOR substrate p70 S6 kinase abrogated PAK1 phosphorylation and enhanced HCV RNA abundance, whereas overexpression of a constitutively active alternate substrate, eukaryotic translation initiation factor 4E-binding protein 1, increased cap-independent viral translation and viral RNA abundance without influencing PAK1 phosphorylation. Similar data indicated that mTOR is regulated by both phosphatidylinositol 3-kinase/Akt and ERK. Taken together, the data indicate that p70 S6 kinase activates PAK1 and contributes to phosphatidylinositol 3-kinase- and ERK-mediated regulation of HCV RNA replication.
