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

Zachary C Elmore1, L Patrick Havlik1, Daniel K Oh1

  • 1Department of Surgery, Duke University School of Medicine, Durham, NC, USA.

Nature Communications
|October 30, 2021
PubMed

Insights

Researchers discovered a novel viral protein, membrane-associated accessory protein (MAAP), that acts as a key factor in adeno-associated virus (AAV) secretion. MAAP facilitates AAV release, potentially through association with extracellular vesicles (EVs), offering new avenues for AAV vector engineering.

Area of Science:

  • Virology
  • Molecular Biology
  • Gene Therapy

Background:

  • Adeno-associated viruses (AAV) require helper viruses for lytic infection.
  • Mechanisms for AAV pre-lytic secretion as free or extracellular vesicle (EV)-associated particles are not well understood.

Purpose of the Study:

  • To identify and characterize novel viral factors involved in adeno-associated virus (AAV) secretion.
  • To elucidate the role of the membrane-associated accessory protein (MAAP) in AAV egress and to explore its potential for AAV vector engineering.

Main Methods:

  • Identification and characterization of the membrane-associated accessory protein (MAAP) from a frameshifted open reading frame within the AAV cap gene.
  • Analysis of wild-type and mutated AAV (MAAPΔ) secretion levels.
  • Trans-complementation experiments to restore MAAP function.
  • Investigation of AAV association with extracellular vesicles (EVs) using various processing and analytical methods.

Main Results:

  • MAAP was identified as a novel viral egress factor essential for AAV secretion.
  • A conserved cationic amphipathic domain within MAAP is critical for its function.
  • Mutating the MAAP start site (MAAPΔ) significantly attenuated AAV secretion and increased intracellular retention.
  • Trans-complementation with MAAP restored secretion of MAAPΔ AAV serotypes.
  • Evidence suggests MAAP promotes viral egress through association with EVs.

Conclusions:

  • MAAP is a newly discovered viral egress factor that significantly enhances adeno-associated virus (AAV) secretion.
  • MAAP's function is linked to its cationic amphipathic domain and its role in AAV association with extracellular vesicles (EVs).
  • MAAP represents a potential platform for engineering AAV vectors and modulating the secretion of other EV-associated cargo.

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