title: Some mechanisms of FLIP expression in inhibition of HIV-1 replication in Jurkat cells, CD4+ T cells and PBMCs.
abstract: 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.
authors.affiliation: Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.
authors.forename: Jiying
authors.initials: J
authors.lastname: Tan
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Krishnakumar
authors.initials: K
authors.lastname: Devadas
authors.forename: Jiangqin
authors.initials: J
authors.lastname: Zhao
authors.forename: Panhe
authors.initials: P
authors.lastname: Zhang
authors.forename: Indira
authors.initials: I
authors.lastname: Hewlett
mesh_terms: D000071480:APOBEC-3G Deaminase; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000090103:Antiviral Restriction Factors; D017209:Apoptosis / Q000235:genetics; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics*; D015536:Down-Regulation; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000235:genetics / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology*; D020935:MAP Kinase Signaling System / Q000235:genetics; D021962:Membrane Microdomains / Q000235:genetics / Q000378:metabolism / Q000821:virology; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation; D014779:Virus Replication / Q000235:genetics*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D000071480:APOBEC-3G Deaminase; D015703:Antigens, CD; D000090103:Antiviral Restriction Factors; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins; D053181:Caspase 8; D003564:Cytidine Deaminase; D053200:Fas-Associated Death Domain Protein; D058851:GPI-Linked Proteins; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D051839:NFI Transcription Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514793:gp120 protein, Human immunodeficiency virus 1; C514799:p24 protein, Human Immunodeficiency Virus Type 1; C477346:TRIM5 protein, human; C464924:APOBEC3G protein, human