AAV2 X increases AAV6 rep/cap-driven rAAV production

被引:9
作者
Cao, M. [1 ]
Chiriva-Internati, M. [2 ]
Hermonat, P. L. [1 ,3 ]
机构
[1] Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA
[2] Texas Tech Univ, Dept Internal Med, Lubbock, TX 79408 USA
[3] Univ Arkansas Med Sci, Dept Obstet & Gynecol, Little Rock, AR 72205 USA
关键词
Adeno-associated virus type 2; Adeno-associated virus type 6; X protein; X gene; DNA replication; Virion production; Gene therapy; Rep78; protein; Adeno-associated virus type 8; Rolling circle replication; ADENO-ASSOCIATED VIRUS; ADENOASSOCIATED VIRUS; PROTEIN; REP78; GENE; DNA; TRANSDUCTION; VECTORS; MUTANTS; CELLS;
D O I
10.1016/j.virol.2015.03.007
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We have recently identified a new gene, involved in DNA replication, at the far 3' end of the adeno-associated virus type 2 (AAV2) genome. The AAV type 6 (AAV6) genome has a disrupted X open reading frame (ORF) whose two halves, when combined, have full-length homology and comparable size to AAV2 X. Hypothesizing that AAV6 X is inactive, we assessed if AAV2 X augments recombinant (r)AAV2 DNA replication and virion production, but with rep and cap trans-functions of AAV6. Using AAV2 X expressing HEK293 cell lines we show AAV2 X significantly boosts rAAV DNA replication/virion production, driven by AAV6 rep/cap as it does the AAV2 rep/cap system. Protein BLAST search for homology between AAV2 X and various AAV Rep78 proteins suggests that X might be AAV8 Rep 78-derived and have some of its activities. These data suggest that AAV2 X, and the corresponding X genes of other AAV types/clades, warrant further study. Published by Elsevier Inc.
引用
收藏
页码:84 / 88
页数:5
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