Down-regulation of HIV-1 Infection by Inhibition of the MAPK Signaling Pathway

• 作 者: Jian Gong Xi-hui Shen Chao Che
• 机 构: The State Key Laboratory of Virology,School of Life Science
• 出 处: 中国病毒学
• 发表日期: 2004年期
• 关键词: HIV-1 inhibition Mitogen-activated protein kinase(MAPK) Extracellular signal-reg
• 基金项目: Key Projects in the National Science and Technology Pillar Program during the Eleventh Five-Year Plan Period of China;Major Science and Technology Innovation Cross Project of the Chinese Academy of Sc

The human immunodeficiency virus type 1(HIV-1)can interact with and exploit the host cellular machinery to replicate and propagate itself.Numerous studies have shown that the Mitogen-activated protein kinase(MAPK)signal pathway can positively regulate the replication of HIV-1,but exactly how each MAPK pathway affects HIV-1 infection and replication is not understood.In this study,we used the Extracellular signal-regulated kinase(ERK)pathway inhibitor,PD98059,the Jun N-terminal kinase(JNK)pathway inhibitor,SP600125,and the p38 pathway inhibitor,SB203580,to investigate the roles of these pathways in HIV-1replication.We found that application of PD98059 results in a strong VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus and HIV-1NL4-3 virus inhibition activity.In addition,SB203580 and SP600125 also elicited marked VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus inhibition activity but no HIV-1NL4-3 virus inhibition activity.We also found that SB203580 and SP600125 can enhance the HIV-1 inhibition activity of PD98059when cells were treated with all three MAPK pathway inhibitors in combination.Finally,we show that HIV-1virus inhibition activity of the MAPK pathway inhibitors was the result of the negative regulation of HIV-1 LTR promoter activity.