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

Zachary C. Elmore, L. Patrick Havlik, Daniel K. Oh, Leif Anderson, George Daaboul, Garth W. Devlin, Heather A. Vincent and Aravind Asokan ()
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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

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26485-4

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