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. 2011 Apr 7;26(2):114–122. doi: 10.1007/s12250-011-3184-y

Down-regulation of HIV-1 infection by inhibition of the MAPK signaling pathway

Jian Gong 1,2, Xi-hui Shen 1, Chao Chen 1, Hui Qiu 1, Rong-ge Yang 1,✉
PMCID: PMC8222497  PMID: 21468934

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-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 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.

Key words: HIV-1 inhibition, Mitogen-activated protein kinase (MAPK), Extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), p38, LTR activation

Footnotes

Foundation items: Key Projects in the National Science and Technology Pillar Program during the Eleventh Five-Year Plan Period of China (2008ZX10001-002); Major Science and Technology Innovation Cross Project of the Chinese Academy of Sciences (KSCX1-YW-10).

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