PMID- 22514350
OWN - NLM
STAT- MEDLINE
DCOM- 20120815
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 86
IP  - 13
DP  - 2012 Jul
TI  - Identification of the galactose binding domain of the adeno-associated virus 
      serotype 9 capsid.
PG  - 7326-33
LID - 10.1128/JVI.00448-12 [doi]
AB  - Adeno-associated virus serotype 9 (AAV9) vectors show promise for gene therapy of 
      a variety of diseases due to their ability to transduce multiple tissues, 
      including heart, skeletal muscle, and the alveolar epithelium of the lung. In 
      addition, AAV9 is unique compared to other AAV serotypes in that it is capable of 
      surpassing the blood-brain barrier and transducing neurons in the brain and 
      spinal cord. It has recently been shown that AAV9 uses galactose as a receptor to 
      transduce many different cell types in vitro, as well as cells of the mouse 
      airway in vivo. In this study, we sought to identify the specific amino acids of 
      the AAV9 capsid necessary for binding to galactose. By site-directed mutagenesis 
      and cell binding assays, plus computational ligand docking studies, we discovered 
      five amino acids, including N470, D271, N272, Y446, and W503, which are required 
      for galactose binding that form a pocket at the base of the protrusions around 
      the icosahedral 3-fold axes of symmetry. The importance of these amino acids for 
      tissue tropism was also confirmed by in vivo studies in the mouse lung. 
      Identifying the interactions necessary for AAV9 binding to galactose may lead to 
      advances in vector engineering.
FAU - Bell, Christie L
AU  - Bell CL
AD  - Gene Therapy Program, Department of Pathology and Laboratory Medicine, Perelman 
      School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, 
      USA.
FAU - Gurda, Brittney L
AU  - Gurda BL
FAU - Van Vliet, Kim
AU  - Van Vliet K
FAU - Agbandje-McKenna, Mavis
AU  - Agbandje-McKenna M
FAU - Wilson, James M
AU  - Wilson JM
LA  - eng
GR  - P01 HL059407/HL/NHLBI NIH HHS/United States
GR  - P01 HL059412/HL/NHLBI NIH HHS/United States
GR  - R01 GM082946/GM/NIGMS NIH HHS/United States
GR  - T32 DK007748/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120418
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Capsid Proteins)
RN  - 0 (Mutant Proteins)
RN  - 0 (hexon capsid protein, Adenovirus)
RN  - X2RN3Q8DNE (Galactose)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Binding Sites
MH  - CHO Cells
MH  - Capsid Proteins/*genetics/*metabolism
MH  - Cricetinae
MH  - Dependovirus/*genetics/physiology
MH  - Galactose/*metabolism
MH  - Lung/virology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutagenesis, Site-Directed
MH  - Mutant Proteins/genetics/metabolism
MH  - Virus Attachment
PMC - PMC3416318
EDAT- 2012/04/20 06:00
MHDA- 2012/08/16 06:00
PMCR- 2013/01/01
CRDT- 2012/04/20 06:00
PHST- 2012/04/20 06:00 [entrez]
PHST- 2012/04/20 06:00 [pubmed]
PHST- 2012/08/16 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - JVI.00448-12 [pii]
AID - 00448-12 [pii]
AID - 10.1128/JVI.00448-12 [doi]
PST - ppublish
SO  - J Virol. 2012 Jul;86(13):7326-33. doi: 10.1128/JVI.00448-12. Epub 2012 Apr 18.