Objective To investigate whether the nonstructural protein 5A(NS5A) encoded by the human hepatitis C virus RNA genome could affect the expression of TLR4.Methods HCV NS5A expression plasmid(pCN5A) was transfected into QSG7701 cells using a lipofectin reagent and the HCV NS5A protein was detected using immuno-histochemistry staining.TLR4 mRNA was evaluated by reverse transcriptase polymerase chain reaction(RT-PCR).Results HCV NS5A was detected in the cytoplasm of the QSG7701 cells transfected with pCN5A,the expression of TLR4 mRNA and protein were both up-regulated in the presence of the HCV NS5A protein.Conclusion HCV NS5A stimulates the transcription of TLR4 mRNA and the expression of TLR4 protein.
[1]Mamta K,Jain,He-Jun Yuan,Beverley Admams-Huet,et al.Pegylated Interferon and Ribavirin Promote EarlyEvolution of Nonstructural 5A Protein in Individualswith Hepatitis C Who Demonstrate a Response toTreatment[J].J Infect Dis,2009,200(6):866-876.
|
[2]Thomas A,Laxton C,Rodman J,et al.Investigating Toll-like receptor agonists for potential to treat hepatitis Cvirus infection[J].Antimicrob Agents Chemother,2007,51(8):2969-2978.
|
[3]Gong G,Waris G,Tanveer R,et al.Human hepatitisCvirus NS5A protein alters intracellular calcium levels,induces oxidative stress,and activates STAT-3andNF-kappa B[J].Proc Natl Acad Sci USA,2001,98(17):9599-9604.
|
[4]赵甫涛,姬新颖,潘蕾,等.Toll样受体及其在病毒性肝炎发病机制中的作用[J].世界华人消化杂志,2005,13(20):2459-2463.
|
[5]白雪帆,姜泓.Toll样受体4介导的抗病毒免疫[J].内科理论与实践,2007,2(4):220-223.
|
[6]Perrin-Cocon L,Agaugue S,Diaz O,et al.Th1 disabledfunction in response to TLR4 stimulation of monocyte-derived DC from patients chronically-infected byhepatitis C virus[J].Plos One,2008,3(5):e2260.
|
[7]Agaugue S,Perrin-Cocon L,Andre P,et al.HepatitisC lipo-viro-particle form chronically infected patientsinterferes with TLR4 signaling in dendritic cell[J].PlosOne,2007,2(3):e330.
|
[8]Bobardt MD,Cheng G,de Witte L,et al.Hepatitis C virusNS5A anchor peptide disrupts human immunodeficiencyvirus[J].Proc Natl Acad Sci USA,2008,105(14):5525-5530.
|
[9]Mahchida K,Cheng KT Sung VM,et al.Hepatites Cvirus induces toll-like receptor 4 expression,leading toenhanced production of beta interferon and interleukin-6[J].J Virol,2006,80(2):866-874.
|
[10]Mozer-Lisewsika I,Sluzewski W,Kackzmarek M,etal.Tissue localization of Toll-like receptors in biopsysepecimens of liver from hepatitis C virus[J].Scand JImmunol,2005,62(4):407-412.
|
[11]郭云蔚,尉秀清,李永伟,等.Toll样受体4在乙型肝炎组织及细胞株HepG2/HepG2.2.15内的表达特征[J].中山大学学报(医学科学版),2007,28(3):284-287.
|