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bioRxiv · 10.1101/2021.06.17.448857

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

Elmore, Z.·Havlik, L. P.·Oh, D. K.·Vincent, H. A.·Asokan, A.
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Abstract

Adeno-associated viruses (AAV) rely on helper viruses to transition from latency to lytic infection. Some recombinant AAV serotypes are secreted in a pre-lytic manner as extracellular vesicle (EV)-associated particles, although mechanisms underlying such are unknown. Here, we discover that the membrane-associated accessory protein (MAAP), expressed from a (+1) frameshifted open reading frame (ORF) in the AAV capsid (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 (MAAP{Delta}) show markedly attenuated secretion and correspondingly, increased intracellular retention. Trans-complementation with recombinant MAAP restored extracellular secretion of multiple AAV/MAAP{Delta} serotypes. MAAP is sorted into recycling Rab11+ vesicles and strongly associates with EV markers upon fractionation. In addition to characterizing a novel viral egress factor, these studies highlight a prospective engineering platform to modulate secretion of AAV vectors or other EV-associated cargo.

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Elmore, Z., Havlik, L. P., Oh, D. K., Vincent, H. A., Asokan, A.. 2021-06-17. The membrane associated accessory protein is an adeno-associated viral egress factor. https://doi.org/10.1101/2021.06.17.448857

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