title: Some findings of FADD knockdown in inhibition of HIV-1 replication in Jurkat cells and PBMCs.
abstract: Fas-associated protein with death domain (FADD) is a key adaptor molecule transmitting the death signal mediated by death receptors, and it is also required for T cell proliferation. A recent study indicated that FADD is able to affect HIV-1 production, but the mechanism is not known. Using the susceptible Jurkat cell line and peripheral blood mononuclear cells, we studied the effects of FADD on HIV-1 production. TaqMan RT-PCR was used to quantify HIV-1 viral RNA copies, and Western blot analysis was used to detect protein expression. FADD knockdown decreased HIV-1 replication and inactivated caspase-3 activity in the cells and blocked CD4 translocation to the lipid rafts of the plasma membrane. Reduced expression of FADD suppressed TCR signaling through downregulation of TCR, CD3, and Zap-70 in response to HIV-1 infection and blocked the trafficking of TCR, CD3, CD28, and Zap-70 to lipid rafts, leading to reduced activation of NF-κB and NFAT, which are required for HIV-1 replication. FADD knockdown diminished caspase-8 migration to lipid rafts and its expression in response to HIV-1 infection. These results indicate that FADD, as a host pro-apoptotic protein, plays important roles in regulating HIV-1 replication and production in several ways, and apoptotic pathway inhibition is able to decrease HIV-1 replication and production.
authors.affiliation: Lab of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Building 29B, Rm 4NN22 8800 Rockville Pike, Bethesda, MD, 20892, USA, xue.wang@fda.hhs.gov.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Jiying
authors.initials: J
authors.lastname: Tan
authors.forename: Jiangqin
authors.initials: J
authors.lastname: Zhao
authors.forename: Viswannath
authors.initials: V
authors.lastname: Ragupathy
authors.forename: Mohan
authors.initials: M
authors.lastname: Haleyurgirisetty
authors.forename: Indira
authors.initials: I
authors.lastname: Hewlett
mesh_terms: D049109:Cell Proliferation / Q000235:genetics; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D015658:HIV Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*
chemical_list: C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein
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