title: Down-regulation of HIV-1 infection by inhibition of the MAPK signaling pathway.
abstract: 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-1 replication. We found that application of PD98059 results in a strong VSV-G pseudotyped HIV-1(NL4-3) luciferase reporter virus and HIV-1(NL4-3) virus inhibition activity. In addition, SB203580 and SP600125 also elicited marked VSV-G pseudotyped HIV-1(NL4-3) luciferase reporter virus inhibition activity but no HIV-1(NL4-3) virus inhibition activity. We also found that SB203580 and SP600125 can enhance the HIV-1 inhibition activity of PD98059 when cells were treated with all three MAPK pathway inhibitors in combination. Finally, we show that HIV-1 virus inhibition activity of the MAPK pathway inhibitors was the result of the negative regulation of HIV-1 LTR promoter activity.
authors.affiliation: Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gong
authors.forename: Xi-hui
authors.initials: XH
authors.lastname: Shen
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Qiu
authors.forename: Rong-ge
authors.initials: RG
authors.lastname: Yang
mesh_terms: D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D015658:HIV Infections / Q000201:enzymology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D047428:Protein Kinase Inhibitors; D020928:Mitogen-Activated Protein Kinases