Functional roles of the membrane-associated AAV protein MAAP
Abstract With a limited coding capacity of 4.7 kb, adeno-associated virus (AAV) genome has evolved over-lapping 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 a...
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Nature Portfolio
2021
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oai:doaj.org-article:cfb778447b9c4cc69e2061b9fd4811662021-11-08T10:46:27ZFunctional roles of the membrane-associated AAV protein MAAP10.1038/s41598-021-01220-72045-2322https://doaj.org/article/cfb778447b9c4cc69e2061b9fd4811662021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01220-7https://doaj.org/toc/2045-2322Abstract With a limited coding capacity of 4.7 kb, adeno-associated virus (AAV) genome has evolved over-lapping 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 different reading frame. This 13 KDa protein, unique to the dependovirus genus, is not homologous to any known protein. Our studies confirm that MAAP translation initiates from the first 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 affected 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 modifications led to increased packaging of contaminating, non-viral DNA. Our results show that MAAP plays a significant role in AAV infection, with profound implications for the production of therapeutic AAV vectors.Lionel GalibertAmira HyvönenReetta A. E. ErikssonSalla MattolaVesa AhoSami SalminenJustin D. AlbersSanna K. PeltolaSaija WemanTiina NieminenSeppo Ylä-HerttualaHanna P. LeschMaija Vihinen-RantaKari J. AirenneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021) |
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DOAJ |
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Medicine R Science Q Lionel Galibert Amira Hyvönen Reetta A. E. Eriksson Salla Mattola Vesa Aho Sami Salminen Justin D. Albers Sanna K. Peltola Saija Weman Tiina Nieminen Seppo Ylä-Herttuala Hanna P. Lesch Maija Vihinen-Ranta Kari J. Airenne Functional roles of the membrane-associated AAV protein MAAP |
| description |
Abstract With a limited coding capacity of 4.7 kb, adeno-associated virus (AAV) genome has evolved over-lapping 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 different reading frame. This 13 KDa protein, unique to the dependovirus genus, is not homologous to any known protein. Our studies confirm that MAAP translation initiates from the first 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 affected 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 modifications led to increased packaging of contaminating, non-viral DNA. Our results show that MAAP plays a significant role in AAV infection, with profound implications for the production of therapeutic AAV vectors. |
| format |
article |
| author |
Lionel Galibert Amira Hyvönen Reetta A. E. Eriksson Salla Mattola Vesa Aho Sami Salminen Justin D. Albers Sanna K. Peltola Saija Weman Tiina Nieminen Seppo Ylä-Herttuala Hanna P. Lesch Maija Vihinen-Ranta Kari J. Airenne |
| author_facet |
Lionel Galibert Amira Hyvönen Reetta A. E. Eriksson Salla Mattola Vesa Aho Sami Salminen Justin D. Albers Sanna K. Peltola Saija Weman Tiina Nieminen Seppo Ylä-Herttuala Hanna P. Lesch Maija Vihinen-Ranta Kari J. Airenne |
| author_sort |
Lionel Galibert |
| title |
Functional roles of the membrane-associated AAV protein MAAP |
| title_short |
Functional roles of the membrane-associated AAV protein MAAP |
| title_full |
Functional roles of the membrane-associated AAV protein MAAP |
| title_fullStr |
Functional roles of the membrane-associated AAV protein MAAP |
| title_full_unstemmed |
Functional roles of the membrane-associated AAV protein MAAP |
| title_sort |
functional roles of the membrane-associated aav protein maap |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/cfb778447b9c4cc69e2061b9fd481166 |
| work_keys_str_mv |
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