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Some mechanisms of FLIP expression in inhibition of HIV‐1 replication in Jurkat cells, CD4+ T cells and PBMCs
Author(s) -
Tan Jiying,
Wang Xue,
Devadas Krishnakumar,
Zhao Jiangqin,
Zhang Panhe,
Hewlett Indira
Publication year - 2013
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24397
Subject(s) - jurkat cells , tetherin , biology , microbiology and biotechnology , viral replication , fadd , samhd1 , apoptosis , virology , t cell , programmed cell death , caspase , virus , immune system , immunology , reverse transcriptase , rna , gene , biochemistry
HIV‐1 infection and replication are affected by host factors. Recent studies demonstrate that molecules from apoptotic pathways regulate HIV‐1 replication. Therefore, studies on effects of host factors that maintain host cell survival and influence HIV‐1 replication are critical to understanding the mechanisms of HIV‐1 replicative cycle. Using the susceptible Jurkat cell line, CD4 + T cells, and peripheral blood mononuclear cells (PBMCs), we studied the role of FLIP, an inhibitor of caspase‐8, in HIV‐1 production. Full length cellular FLIP (cFLIP) inhibited HIV‐1 replication in these cells. cFLIP upregulated the expression of viral restriction factors, such as TRIM5, Apobec3G, and Bst2/tetherin, decreased nuclear factor 1C expression and inactivated ERK and p38 induced by HIV‐1 in Jurkat cells. cFLIP blocked the trafficking of gp120 and Gag p24 capsid protein into lipid rafts with inhibition of Tsg101 and Alix in ESCRT signaling pathway. cFLIP also promoted Bst2/tetherin trafficking into lipid rafts. These results indicate that cFLIP may inhibit the HIV‐1 replication cycle at multiple steps, including viral RNA release, transcription, traffic and assembly. We also found that cFLIP expression downregulated Fas expression and inactivated FADD in the Fas‐mediated apoptotic pathway. The inactivated FADD also inhibited HIV‐1 replication. J. Cell. Physiol. 228: 2305–2313, 2013. © 2013 Wiley Periodicals, Inc.