1. GB virus type C E2 protein inhibits human immunodeficiency virus type 1 Gag assembly by downregulating human ADP-ribosylation factor 1.
- Author
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Wang C, Timmons CL, Shao Q, Kinlock BL, Turner TM, Iwamoto A, Zhang H, Liu H, and Liu B
- Subjects
- Blotting, Western, Coinfection virology, Down-Regulation, Fluorescent Antibody Technique, HEK293 Cells, HeLa Cells, Humans, Microscopy, Confocal, Real-Time Polymerase Chain Reaction, Transfection, Virus Assembly physiology, Virus Release physiology, ADP-Ribosylation Factor 1 metabolism, HIV-1 metabolism, Viral Envelope Proteins metabolism, gag Gene Products, Human Immunodeficiency Virus metabolism
- Abstract
GB virus type C (GBV-C) glycoprotein E2 protein disrupts HIV-1 assembly and release by inhibiting Gag plasma membrane targeting, however the mechanism by which the GBV-C E2 inhibits Gag trafficking remains unclear. In the present study, we identified ADP-ribosylation factor 1 (ARF1) contributed to the inhibitory effect of GBV-C E2 on HIV-1 Gag membrane targeting. Expression of GBV-C E2 decreased ARF1 expression in a proteasomal degradation-dependent manner. The restoration of ARF1 expression rescued the HIV-1 Gag processing and membrane targeting defect imposed by GBV-C E2. In addition, GBV-C E2 expression also altered Golgi morphology and suppressed protein traffic through the secretory pathway, which are all consistent with a phenotype of disrupting the function of ARF1 protein. Thus, our results indicate that GBV-C E2 inhibits HIV-1 assembly and release by decreasing ARF1, and may provide insights regarding GBV-C E2's potential for a new therapeutic approach for treating HIV-1.
- Published
- 2015
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