title: GB virus type C E2 protein inhibits human immunodeficiency virus type 1 Gag assembly by downregulating human ADP-ribosylation factor 1.
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.
authors.affiliation: Center for AIDS Health Disparities Research, Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee, USA.|Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Clinical Laboratory, Guangdong Institute of Gastroenterology and The Sixth Affiliated Hospital, Institute of Human Virology and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Chenliang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Center for AIDS Health Disparities Research, Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Timmons
authors.affiliation: Center for AIDS Health Disparities Research, Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Qiujia
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Center for AIDS Health Disparities Research, Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Ballington L
authors.initials: BL
authors.lastname: Kinlock
authors.affiliation: Center for AIDS Health Disparities Research, Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Turner
authors.affiliation: Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Aikichi
authors.initials: A
authors.lastname: Iwamoto
authors.affiliation: Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Clinical Laboratory, Guangdong Institute of Gastroenterology and The Sixth Affiliated Hospital, Institute of Human Virology and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Clinical Laboratory, Guangdong Institute of Gastroenterology and The Sixth Affiliated Hospital, Institute of Human Virology and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Huanliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Center for AIDS Health Disparities Research, Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Bindong
authors.initials: B
authors.lastname: Liu
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism*; D015153:Blotting, Western; D060085:Coinfection / Q000821:virology; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D014759:Viral Envelope Proteins / Q000378:metabolism*; D019065:Virus Assembly / Q000502:physiology; D057074:Virus Release / Q000502:physiology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D014759:Viral Envelope Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C107619:glycoprotein E2, GB virus C; D020823:ADP-Ribosylation Factor 1
keywords: ARF1; GBV-C E2; HIV-1 Gag; HIV-1 assembly; Immune response; Immunity; Immunology and Microbiology Section; plasma membrane targeting