The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity.
The unique region of the VP1 protein of parvoviruses was proposed to contain a parvoviral phospholipase A2 (pvPLA2) motif. Here, PLA2 activity is shown in the unique region of adeno-associated virus type 2 (AAV-2) VP1 when expressed as an isolated domain in bacteria. Mutations in this region of the capsid protein strongly reduced the infectivity of mutant virions in comparison to wild-type AAV-2. This correlated with effects on the activity of PLA2. The mutations had no influence on capsid assembly, packaging of viral genomes into particles or binding to and entry into HeLa cells. However, a delayed onset and reduced amount of early gene expression, as measured by Rep immunofluorescence, was observed. These results suggest that pvPLA2 activity is required for a step following perinuclear accumulation of virions but prior to early gene expression.
Girod
Anne
A
Laboratorium für Molekulare Biologie, Genzentrum, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, D-81377 München, Germany1.
Wobus
Christiane E
CE
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany2.
Zádori
Zoltán
Z
Centre de Microbiologie et Biotechnologie, INRS - Institut Armand-Frappier, Université du Québec, 531 boul. des Prairies, Laval, Quebec, Canada H7V 1B73.
Ried
Martin
M
Laboratorium für Molekulare Biologie, Genzentrum, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, D-81377 München, Germany1.
Leike
Kristin
K
Laboratorium für Molekulare Biologie, Genzentrum, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, D-81377 München, Germany1.
Tijssen
Peter
P
Centre de Microbiologie et Biotechnologie, INRS - Institut Armand-Frappier, Université du Québec, 531 boul. des Prairies, Laval, Quebec, Canada H7V 1B73.
Kleinschmidt
Jürgen A
JA
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany2.
Hallek
Michael
M
GSF - National Research Center for Environment and Health, Klinische Kooperationsgruppe Gentherapie, Hämatologikum, Marchioninistrasse 15, D-81377 München, Germany5.|Medizinische Klinik III, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, D-81377 München, Germany4.|Laboratorium für Molekulare Biologie, Genzentrum, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, D-81377 München, Germany1.
D002213:Capsid / Q000502:physiology*; D036022:Capsid Proteins; D000229:Dependovirus / Q000235:genetics / Q000502:physiology*; D015316:Genetic Therapy; D006367:HeLa Cells; D006801:Humans; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D019065:Virus Assembly
D036022:Capsid Proteins; D010741:Phospholipases A; D054467:Phospholipases A2