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dc.contributor.authorGalibert, Lionel
dc.contributor.authorHyvönen, Amira
dc.contributor.authorEriksson, Reetta A. E.
dc.contributor.authorMattola, Salla
dc.contributor.authorAho, Vesa
dc.contributor.authorSalminen, Sami
dc.contributor.authorAlbers, Justin D.
dc.contributor.authorPeltola, Sanna K.
dc.contributor.authorWeman, Saija
dc.contributor.authorNieminen, Tiina
dc.contributor.authorYlä-Herttuala, Seppo
dc.contributor.authorLesch, Hanna P.
dc.contributor.authorVihinen-Ranta, Maija
dc.contributor.authorAirenne, Kari J.
dc.date.accessioned2021-11-08T07:46:07Z
dc.date.available2021-11-08T07:46:07Z
dc.date.issued2021
dc.identifier.citationGalibert, L., Hyvönen, A., Eriksson, R. A. E., Mattola, S., Aho, V., Salminen, S., Albers, J. D., Peltola, S. K., Weman, S., Nieminen, T., Ylä-Herttuala, S., Lesch, H. P., Vihinen-Ranta, M., & Airenne, K. J. (2021). Functional roles of the membrane-associated AAV protein MAAP. <i>Scientific Reports</i>, <i>11</i>, Article 21698. <a href="https://doi.org/10.1038/s41598-021-01220-7" target="_blank">https://doi.org/10.1038/s41598-021-01220-7</a>
dc.identifier.otherCONVID_101767073
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/78516
dc.description.abstractWith a limited coding capacity of 4.7 kb, adeno-associated virus (AAV) genome has evolved overlapping genes to maximise the usage of its genome. An example is the recently found ORF in the cap gene, encoding membrane-associated accessory protein (MAAP), located in the same genomic region as the VP1/2 unique domain, but in a diferent reading frame. This 13 KDa protein, unique to the dependovirus genus, is not homologous to any known protein. Our studies confrm that MAAP translation initiates from the frst CTG codon found in the VP1 ORF2. We have further observed MAAP localised in the plasma membrane, in the membranous structures in close proximity to the nucleus and to the nuclear envelope by co-transfecting with plasmids encoding the wild-type AAV (wt-AAV) genome and adenovirus (Ad) helper genes. While keeping VP1/2 protein sequence identical, both inactivation and truncation of MAAP translation afected the emergence and intracellular distribution of the AAV capsid proteins. We have demonstrated that MAAP facilitates AAV replication and has a role in controlling Ad infection. Additionally, we were able to improve virus production and capsid integrity through a C-terminal truncation of MAAP while other modifcations led to increased packaging of contaminating, non-viral DNA. Our results show that MAAP plays a signifcant role in AAV infection, with profound implications for the production of therapeutic AAV vectors.en
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofseriesScientific Reports
dc.rightsCC BY 4.0
dc.titleFunctional roles of the membrane-associated AAV protein MAAP
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202111085539
dc.contributor.laitosBio- ja ympäristötieteiden laitosfi
dc.contributor.laitosDepartment of Biological and Environmental Scienceen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.description.reviewstatuspeerReviewed
dc.relation.issn2045-2322
dc.relation.volume11
dc.type.versionpublishedVersion
dc.rights.copyright© The Author(s) 2021
dc.rights.accesslevelopenAccessfi
dc.relation.grantnumber330896
dc.subject.ysokapsidi
dc.subject.ysoproteiinit
dc.subject.ysoparvovirukset
dc.subject.ysoinfektiot
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p28020
jyx.subject.urihttp://www.yso.fi/onto/yso/p4332
jyx.subject.urihttp://www.yso.fi/onto/yso/p21764
jyx.subject.urihttp://www.yso.fi/onto/yso/p7316
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.1038/s41598-021-01220-7
dc.relation.funderSuomen Akatemiafi
dc.relation.funderAcademy of Finlanden
jyx.fundingprogramAkatemiahanke, SAfi
jyx.fundingprogramAcademy Project, AoFen
jyx.fundinginformationThis work was financed by the Kuopio Center for Gene and Cell Therapy (LG, AH, RAEE, SP, JDA, SW, TN, HPL, KJA), the Jane and Aatos Erkko Foundation (MVR), Academy of Finland under the Award Number 330896 (MVR), and the Graduate School of the University of Jyväskylä (SM).


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