title: Gp120 binding with DC-SIGN induces reactivation of HIV-1 provirus via the NF-κB signaling pathway.
abstract: The reactivation mechanism of latent human immunodeﬁciency virus type 1 (HIV-1) infection is unclear, especially in dendritic cells (DC). DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) binds with HIV-1 and other pathogens to activate the extracellular regulated protein kinase (ERK) and nuclear factor-kappa B (NF-κB) pathways and regulate cytokine expression. We hypothesized that DC-SIGN-induced signaling pathways may activate HIV-1 provirus. To investigate this hypothesis, we generated a model by transfecting 293T cells with a DC-SIGN expression plasmid and an HIV-1 5' long terminal repeat (LTR) reporter plasmid, and then stimulated the 293T cells with HIV-1 gp120 protein, wild-type HIV-1 or VSV-G-pNL4.3 pseudotype virus (without gp120 protein). It was found that the HIV-1 5'LTR was reactivated by HIV-1 gp120 in DC-SIGN-expressing 293T cells. Then the HIV-1 chronically infected CEM-Bru cells were transfected with DC-SIGN expression plasmid and stimulated by HIV-1 gp120 protein. It was found that early and late HIV-1 provirus replication was reactivated by the HIV-1 gp120/DC-SIGN stimulation. We then investigated the involvement of the ERK, p38 mitogen-activated protein kinases and NF-κB signaling pathways in HIV-1 gp120/DC-SIGN-induced activation of HIV-1 provirus by inhibiting the pathways specifically. Our results indicated that HIV-1 gp120/DC-SIGN stimulation reactivates latent HIV-1 provirus via the NF-κB signal pathway.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Changzhong
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Infectious Disease, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Linfang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Fumin
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China flwnp2013@163.com.
authors.forename: Nanping
authors.initials: N
authors.lastname: Wu
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D011533:Proviruses / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D014779:Virus Replication; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; D037181:Lectins, C-Type; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: DC; DC-SIGN; HIV-1; NF-κB; signaling pathways; viral latency
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