Intrinsic phospholipase A2 activity of adeno-associated virus is involved in endosomal escape of incoming particles.
The unique region of the VP1 capsid protein of adeno-associated viruses (AAV) in common with autonomously replicating parvoviruses comprises a secreted phospholipase A2 (sPLA2) homology domain. While the sPLA2 domain of Minute Virus of Mice has recently been shown to mediate endosomal escape by lipolytic pore formation, experimental evidence for a similar function in AAV infection is still lacking. Here, we explored the function of the sPLA2 domain of AAV by making use of the serotype 2 mutant (76)HD/AN. The sPLA2 defect in (76)HD/AN, which severely impairs AAV's infectivity, could be complemented in trans by co-infection with wild-type AAV2. Furthermore, co-infection with endosomolytically active, but not with inactive adenoviral variants partially rescued (76)HD/AN, providing the first evidence for a function of this domain in endosomal escape of incoming AAV particles.
Department I of Internal Medicine, University of Cologne, 50924 Cologne, Germany. schlemms@uni-koeln.de
Stefanie
S
Stahnke
Kerstin
K
Lux
Silke
S
Uhrig
Florian
F
Kreppel
Marianna
M
Hösel
Oliver
O
Coutelle
Manfred
M
Ogris
Michael
M
Hallek
Hildegard
H
Büning
D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D000229:Dependovirus / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D011992:Endosomes / Q000502:physiology / Q000821:virology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D054467:Phospholipases A2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012703:Serotyping; D014771:Virion / Q000378:metabolism*
D036022:Capsid Proteins; D054467:Phospholipases A2