About: A Two-hybrid Screen Identifies Cathepsins B and L as Uncoating Factors for Adeno-associated Virus 2 and 8

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About: A Two-hybrid Screen Identifies Cathepsins B and L as Uncoating Factors for Adeno-associated Virus 2 and 8 Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	A Two-hybrid Screen Identifies Cathepsins B and L as Uncoating Factors for Adeno-associated Virus 2 and 8
Creator	Akache, Bassel Fuess, Sally Grimm, Dirk Park, Julie Shen, Xuan Glazer, Dariya Kay, Mark Yant, Stephen
Source	Elsevier; Medline; PMC
abstract	Vectors based on different serotypes of adeno-associated virus hold great promise for human gene therapy, based on their unique tissue tropisms and distinct immunological profiles. A particularly interesting candidate is AAV8, which can efficiently and rapidly transduce a wide range of tissues in vivo. To further unravel the mechanisms behind AAV8 transduction, we used yeast two-hybrid analyses to screen a mouse liver complementary DNA library for cellular proteins capable of interacting with the viral capsid proteins. In total, we recovered approximately 700 clones, comprising over 300 independent genes. Sequence analyses revealed multiple hits for over 100 genes, including two encoding the endosomal cysteine proteases cathepsins B and L. Notably, these two proteases also physically interacted with the corresponding portion of the AAV2 capsid in yeast, but not with AAV5. We demonstrate that cathepsins B and L are essential for efficient AAV2- and AAV8-mediated transduction of mammalian cells, and document the ability of purified cathepsin B and L proteins to bind and cleave intact AAV2 and AAV8 particles in vitro. These data suggest that cathepsin-mediated cleavage could prime AAV capsids for subsequent nuclear uncoating, and indicate that analysis of additional genes recovered in our screen may help to further elucidate the mechanisms behind transduction by AAV8 and related serotypes.
has issue date	2016-12-14(xsd:dateTime)
bibo:doi	10.1038/sj.mt.6300053
bibo:pmid	17235311
has license	no-cc
sha1sum (hex)	44108a4ae274f5b1b2e29d6f1254be02dd5bd447
schema:url	https://doi.org/10.1038/sj.mt.6300053
resource representing a document's title	A Two-hybrid Screen Identifies Cathepsins B and L as Uncoating Factors for Adeno-associated Virus 2 and 8
has PubMed Central identifier	PMC7106033
has PubMed identifier	17235311
schema:publication	Mol Ther
resource representing a document's body	covid:44108a4ae274f5b1b2e29d6f1254be02dd5bd447#body_text
is schema:about of	named entity 'SCREEN' named entity 'CATHEPSINS B' named entity 'VECTORS' named entity 'RANGE' named entity 'DISTINCT' named entity 'RECOVERED' named entity 'DIFFERENT' named entity 'HITS' named entity 'AAV' named entity 'CANDIDATE' named entity 'DOCUMENT ' named entity 'ESSENTIAL' named entity 'REVEALED' named entity 'UNIQUE' named entity 'PRIME' named entity 'VIRAL CAPSID' named entity 'HUMAN GENE' named entity 'CLEAVAGE' named entity 'THESE' named entity '100' named entity 'PARTICLES' named entity 'PROTEINS' named entity 'CELLULAR' named entity 'APPROXIMATELY' named entity 'DNA LIBRARY' covid:arg/44108a4ae274f5b1b2e29d6f1254be02dd5bd447 named entity 'TWO-HYBRID' named entity 'UNCOATING' named entity 'ADENO-ASSOCIATED VIRUS 2' named entity 'SEROTYPES' named entity 'INCLUDING' named entity 'TOTAL' named entity 'YEAST' named entity 'BUT' named entity 'ADDITIONAL' named entity 'BIND' named entity 'ADENO-ASSOCIATED VIRUS' named entity 'HOLD' named entity 'CYSTEINE PROTEASES' named entity 'GENE THERAPY' named entity 'CATHEPSINS B' named entity 'MAMMALIAN' named entity 'CATHEPSIN B' named entity '700' named entity 'TISSUE' named entity 'NUCLEAR' named entity 'MEDIATED' named entity 'INDEPENDENT' named entity 'ENCODING' named entity 'INTACT' named entity 'CAPSID PROTEINS' named entity 'CLONES' named entity 'CAPSIDS' named entity 'MOUSE LIVER' named entity 'IN VIVO' named entity 'TROPISMS' named entity 'CAPABLE' named entity 'RELATED' named entity 'PROTEASES' named entity 'CAPSID' named entity 'PURIFIED' named entity 'PORTION' named entity 'COMPLEMENTARY DNA' named entity 'TISSUES' named entity 'OUR' named entity 'AAV2' named entity 'USED' named entity 'A MOUSE' named entity 'IN VITRO' named entity 'WIDE' named entity 'SUBSEQUENT' named entity '300' named entity 'PROMISE' named entity 'GREAT'

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