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First posted online 30 January 2002 ARTICLE ABSTRACT
Rec 18 September 2001; Acc 21 December 2001 DOI: 10.1099/vir.0.18108-0

The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity

Anne Girod,1 Christiane E. Wobus,2 Zoltán Zádori,3 Martin Ried,1 Kristin Leike,1 Peter Tijssen,3 Jürgen A. Kleinschmidt2 and Michael Hallek1,4,5

1 Laboratorium für Molekulare Biologie, Genzentrum, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, D-81377 München, Germany
2 Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany
3 Centre de Microbiologie et Biotechnologie, INRS – Institut Armand-Frappier, Université du Québec, 531 boul. des Prairies, Laval, Quebec, Canada H7V 1B7
4 Medizinische Klinik III, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, D-81377 München, Germany
5 GSF – National Research Center for Environment and Health, Klinische Kooperationsgruppe Gentherapie, Hämatologikum, Marchioninistrasse 15, D-81377 München, Germany

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.

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© 2002 SGM

This article is now available in the May 2002 print issue of JGV (vol. 83, 973–978). The complete issue of the journal may be seen in electronic form on JGV Online.