Evidence map›Paper›PMID 34716331›Full record

ArticleNature communications2021

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, Aravind Asokan

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
8.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 66 citations in OpenAlex.

  1. Article
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  5. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
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  8. AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
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  11. A novel platform for engineered AAV-based vaccines.Molecular therapy. Methods & clinical development · 2025
    Article
  12. Article
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  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Zachary C ElmoreDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
L Patrick HavlikDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Daniel K OhDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Leif AndersonNanoview Biosciences, Boston, MA, USA.ORCID 0000-0002-0721-7523
George DaaboulNanoview Biosciences, Boston, MA, USA.
Garth W DevlinDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Heather A VincentDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Aravind AsokanDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA. aravind.asokan@duke.edu.ORCID 0000-0001-5563-4877
Duke University · USPrecision BioSciences (United States) · US

Funding

Determinants of AAV TropismR01HL089221 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Aravind Asokan · 2009 to 2026
$8.1M
RE-ENGINEERING AAV GENOME PACKAGINGR01GM127708 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ASOKAN, ARAVIND · 2018 to 2021
$2.0M
CircRNAs and CNS Gene TransferR01NS099371 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ASOKAN, ARAVIND · 2017 to 2021
$1.9M
NHLBI NIH HHS R01 HL089221NIGMS NIH HHS R01 GM127708NINDS NIH HHS R01 NS099371
6 · The paper itself

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.

Indexed as

Virus ReleaseCell MembraneDependovirusExtracellular VesiclesHEK293 CellsHost-Pathogen InteractionsHumansMembrane ProteinsMicroorganisms, Genetically-ModifiedProtein DomainsViral ProteinsMembrane ProteinsViral Proteins

Identifiers

PMID34716331
PMCPMC8556243
OpenAlexW3208075289

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.