Oncotarget

Research Papers: Immunology:

GB virus type C E2 protein inhibits human immunodeficiency virus type 1 Gag assembly by downregulating human ADP-ribosylation factor 1

Chenliang Wang, Christine L. Timmons, Qiujia Shao, Ballington L. Kinlock, Tiffany M. Turner, Aikichi Iwamoto, Hui Zhang, Huanliang Liu and Bindong Liu _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:43293-43309. https://doi.org/10.18632/oncotarget.6537

Metrics: PDF 595 views  |   HTML 974 views  |   ?  


Abstract

Chenliang Wang1,2, Christine L. Timmons1, Qiujia Shao1, Ballington L. Kinlock1, Tiffany M. Turner1, Aikichi Iwamoto3, Hui Zhang2, Huanliang Liu2 and Bindong Liu1

1 Center for AIDS Health Disparities Research, Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee, USA

2 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

3 Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Correspondence to:

Bindong Liu, email:

Huanliang Liu, email:

Keywords: GBV-C E2, HIV-1 assembly, HIV-1 Gag, plasma membrane targeting, ARF1, Immunology and Microbiology Section, Immune response, Immunity

Received: August 15, 2015 Accepted: November 21, 2015 Published: December 09, 2015

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 6537