The membrane associated accessory protein is an adeno-associated viral egress factor.
Journal Article (Journal Article)
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.
- Elmore, ZC; Patrick Havlik, L; Oh, DK; Anderson, L; Daaboul, G; Devlin, GW; Vincent, HA; Asokan, A
- October 29, 2021
Volume / Issue
- 12 / 1
Start / End Page
- 6239 -
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)