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The membrane associated accessory protein is an adeno-associated viral egress factor

Author

Listed:
  • Zachary C. Elmore

    (Duke University School of Medicine)

  • L. Patrick Havlik

    (Duke University School of Medicine)

  • Daniel K. Oh

    (Duke University School of Medicine)

  • Leif Anderson

    (Nanoview Biosciences)

  • George Daaboul

    (Nanoview Biosciences)

  • Garth W. Devlin

    (Duke University School of Medicine)

  • Heather A. Vincent

    (Duke University School of Medicine)

  • Aravind Asokan

    (Duke University School of Medicine
    Duke University School of Medicine
    Duke University
    Duke Regeneration Center, Duke University)

Abstract

Adeno-associated viruses (AAV) rely on helper viruses to transition from latency to lytic infection. Some AAV serotypes are secreted in a pre-lytic manner as free or extracellular vesicle (EV)-associated particles, although mechanisms underlying such are unknown. Here, we discover that the membrane-associated accessory protein (MAAP), expressed from a frameshifted open reading frame in the AAV cap gene, is a novel viral egress factor. MAAP contains a highly conserved, cationic amphipathic domain critical for AAV secretion. Wild type or recombinant AAV with a mutated MAAP start site (MAAPΔ) show markedly attenuated secretion and correspondingly, increased intracellular retention. Trans-complementation with MAAP restored secretion of multiple AAV/MAAPΔ serotypes. Further, multiple processing and analytical methods corroborate that one plausible mechanism by which MAAP promotes viral egress is through AAV/EV association. In addition to characterizing a novel viral egress factor, we highlight a prospective engineering platform to modulate secretion of AAV vectors or other EV-associated cargo.

Suggested Citation

  • Zachary C. Elmore & L. Patrick Havlik & Daniel K. Oh & Leif Anderson & George Daaboul & Garth W. Devlin & Heather A. Vincent & Aravind Asokan, 2021. "The membrane associated accessory protein is an adeno-associated viral egress factor," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26485-4
    DOI: 10.1038/s41467-021-26485-4
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    Cited by:

    1. Trevor J. Gonzalez & Katherine E. Simon & Leo O. Blondel & Marco M. Fanous & Angela L. Roger & Maribel Santiago Maysonet & Garth W. Devlin & Timothy J. Smith & Daniel K. Oh & L. Patrick Havlik & Ruth , 2022. "Cross-species evolution of a highly potent AAV variant for therapeutic gene transfer and genome editing," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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