BKV agnoprotein interacts with α-soluble N-ethylmaleimide-sensitive fusion attachment protein, and negatively influences transport of VSVG-EGFP.

PLoS One

Research Group of Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.

Published: June 2012

Background: The human polyomavirus BK (BKV) infects humans worldwide and establishes a persistent infection in the kidney. The BK virus genome encodes three regulatory proteins, large and small tumor-antigen and the agnoprotein, as well as the capsid proteins VP1 to VP3. Agnoprotein is conserved among BKV, JC virus (JCV) and SV40, and agnoprotein-deficient mutants reveal reduced viral propagation. Studies with JCV and SV40 indicate that their agnoproteins may be involved in transcription, replication and/or nuclear and cellular release of the virus. However, the exact function(s) of agnoprotein of BK virus remains elusive.

Principal Findings: As a strategy of exploring the functions of BKV agnoprotein, we decided to look for cellular interaction partners for the viral protein. Several partners were identified by yeast two-hybrid assay, among them α-SNAP which is involved in disassembly of vesicles during secretion. BKV agnoprotein and α-SNAP were found to partially co-localize in cells, and a complex consisting of agnoprotein and α-SNAP could be co-immunoprecipitated from cells ectopically expressing the proteins as well as from BKV-transfected cells. The N-terminal part of the agnoprotein was sufficient for the interaction with α-SNAP. Finally, we could show that BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter suggesting that agnoprotein may modulate exocytosis.

Conclusions: We have identified the first cellular interaction partner for BKV agnoprotein. The most N-terminal part of BKV agnoprotein is involved in the interaction with α-SNAP. Presence of BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171462PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024489PLOS

Publication Analysis

Top Keywords

bkv agnoprotein
28
agnoprotein
12
bkv
9
jcv sv40
8
cellular interaction
8
agnoprotein α-snap
8
interaction α-snap
8
agnoprotein negatively
8
negatively interferes
8
interferes secretion
8

Similar Publications

Unravelling the Immunomodulatory Effects of Viral Ion Channels, towards the Treatment of Disease.

Viruses

October 2021

Viral Immunology Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 R590 Dublin, Ireland.

The current COVID-19 pandemic has highlighted the need for the research community to develop a better understanding of viruses, in particular their modes of infection and replicative lifecycles, to aid in the development of novel vaccines and much needed anti-viral therapeutics. Several viruses express proteins capable of forming pores in host cellular membranes, termed "Viroporins". They are a family of small hydrophobic proteins, with at least one amphipathic domain, which characteristically form oligomeric structures with central hydrophilic domains.

View Article and Find Full Text PDF

Human neurotropic polyomavirus, JC virus, agnoprotein targets mitochondrion and modulates its functions.

Virology

January 2021

Department of Neuroscience, Laboratory of Molecular Neurovirology, MERB-757, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA. Electronic address:

JC virus encodes an important regulatory protein, known as Agnoprotein (Agno). We have recently reported Agno's first protein-interactome with its cellular partners revealing that it targets various cellular networks and organelles, including mitochondria. Here, we report further characterization of the functional consequences of its mitochondrial targeting and demonstrated its co-localization with the mitochondrial networks and with the mitochondrial outer membrane.

View Article and Find Full Text PDF

A comprehensive proteomics analysis of JC virus Agnoprotein-interacting proteins: Agnoprotein primarily targets the host proteins with coiled-coil motifs.

Virology

January 2020

Department of Neuroscience, Laboratory of Molecular Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA. Electronic address:

JC virus (JCV) Agnoprotein (Agno) plays critical roles in successful completion of the viral replication cycle. Understanding its regulatory roles requires a complete map of JCV-host protein interactions. Here, we report the first Agno interactome with host cellular targets utilizing "Two-Strep-Tag" affinity purification system coupled with mass spectroscopy (AP/MS).

View Article and Find Full Text PDF

Agnoprotein Is an Essential Egress Factor during BK Polyomavirus Infection.

Int J Mol Sci

March 2018

Faculty of Biological Sciences and Astbury Centre for Structural and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.

BK polyomavirus (BKPyV; hereafter referred to as BK) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein.

View Article and Find Full Text PDF

Neuroimmune Regulation of JC Virus by Intracellular and Extracellular Agnoprotein.

J Neuroimmune Pharmacol

June 2018

Department of Neuroscience and Center for Neurovirology, Temple University Lewis Katz School of Medicine, 3500 N. Broad Street, Philadelphia, PA, 19140, USA.

JC virus (JCV) is a human polyomavirus and the etiologic agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). PML is observed in patients with underlying immunocompromising conditions, suggesting that neuro-immune interactions between peripheral immune cells and neuro-glia play an important role in controlling viral reactivation in the brain. There is little known about the immunobiology of JCV reactivation in glial cells and the role of immune, glial, and viral players in this regulation.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!