ATP1B3 Protein Modulates the Restriction of HIV-1 Production and Nuclear Factor κ Light Chain Enhancer of Activated B Cells (NF-κB) Activation by BST-2

• Published in: The Journal of biological chemistry Vol. 291; no. 9; pp. 4754 - 4762
• Main Authors: Nishitsuji, Hironori, Sugiyama, Ryuichi, Abe, Makoto, Takaku, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.02.2016; American Society for Biochemistry and Molecular Biology
• Subjects: Antigens, CD - chemistry; Antigens, CD - genetics; Antigens, CD - metabolism; ATP1B3; bone marrow; BST-2; cell biology; Cell Line; cell surface protein; Fibrillin-1; Fibrillins; Gene Deletion; Gene Expression Regulation; GPI-Linked Proteins - antagonists & inhibitors; GPI-Linked Proteins - chemistry; GPI-Linked Proteins - genetics; GPI-Linked Proteins - metabolism; HEK293 Cells; HeLa Cells; HIV-1 - physiology; human immunodeficiency virus (HIV); Humans; membrane trafficking; Microbiology; Microfilament Proteins - antagonists & inhibitors; Microfilament Proteins - chemistry; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Na+/K+-ATPase; NF-kappa B (NF-KB); NF-kappa B - agonists; NF-kappa B - antagonists & inhibitors; NF-kappa B - genetics; NF-kappa B - metabolism; Protein Interaction Domains and Motifs; Protein Stability; Proteolysis; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; retrovirus; RNA Interference; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors; Sodium-Potassium-Exchanging ATPase - chemistry; Sodium-Potassium-Exchanging ATPase - genetics; Sodium-Potassium-Exchanging ATPase - metabolism; Two-Hybrid System Techniques; Viral Tropism; Virus Replication; BST-2; retrovirus; cell biology; human immunodeficiency virus (HIV); cell surface protein; Na+/K+-ATPase; ATP1B3; NF-kappa B (NF-KB); bone marrow; membrane trafficking
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M115.679357

Here, we identify ATP1B3 and fibrillin-1 as novel BST-2-binding proteins. ATP1B3 depletion in HeLa cells (BST-2-positive cells), but not 293T cells (BST-2-negative cells), induced the restriction of HIV-1 production in a BST-2-dependent manner. In contrast, fibrillin-1 knockdown reduced HIV-1 production in 293T and HeLa cells in a BST-2-independent manner. Moreover, NF-κB activation was enhanced by siATP1B3 treatment in HIV-1- and HIV-1ΔVpu-infected HeLa cells. In addition, ATP1B3 silencing induced high level BST-2 expression on the surface of HeLa cells. These results indicate that ATP1B3 is a co-factor that accelerates BST-2 degradation and reduces BST-2-mediated restriction of HIV-1 production and NF-κB activation.