The Golgi Calcium ATPase Pump Plays an Essential Role in Adeno-associated Virus Trafficking and Transduction

Author:

Madigan Victoria J.12,Berry Garrett E.1,Tyson Tyne O.2,Nardone-White Dasean1,Ark Jonathan3,Elmore Zachary C.2,Murlidharan Giridhar1,Vincent Heather A.2,Asokan Aravind234ORCID

Affiliation:

1. Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

2. Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA

3. Department of Molecular Genetics & Microbiology, Duke University School of Medicine, Durham, North Carolina, USA

4. Department of Biomedical Engineering, Regeneration Next, Duke University, Durham, North Carolina, USA

Abstract

Adeno-associated viruses (AAVs) have proven to be effective gene transfer vectors. However, our understanding of how the host cell environment influences AAV transduction is still evolving. In the present study, we investigated the role of ATP2C1 , which encodes a membrane calcium transport pump, SPCA1, essential for maintaining cellular calcium homeostasis on AAV transduction. Our results indicate that cellular calcium is essential for efficient intracellular trafficking and conformational changes in the AAV capsid that support efficient genome transcription. Further, we show that pharmacological modulation of cellular calcium levels can potentially be applied to improve the AAV gene transfer efficiency.

Funder

HHS | NIH | National Institute of General Medical Sciences

HHS | NIH | National Institute of Neurological Disorders and Stroke

HHS | NIH | National Heart, Lung, and Blood Institute

HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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