Research

The role of myristoylation in the membrane association of the Lassa virus matrix protein Z

Thomas Strecker¹ , Anna Maisa¹ , Stephane Daffis^1,2 , Robert Eichler^1,3 , Oliver Lenz^1,4 and Wolfgang Garten¹

¹  Institut für Virologie der Philipps-Universität Marburg, Hans-Meerwein-Str. 3, 35037 Marburg, Germany

²  Washington University School of Medicine, Department of Infectious Diseases, Box 8051, 660 S. Euclid Avenue, St Louis MO 63110, USA

³  Abbott GmbH & Co KG, Max-Planck-Ring 2, 65205 Wiesbaden, Germany

⁴  Tibotec BVBA, Gen De Wittelaan L 11B 3, 2800 Mechelen, Belgium

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Virology Journal 2006, 3:93doi:10.1186/1743-422X-3-93

Published:	5 November 2006

Abstract

The Z protein is the matrix protein of arenaviruses and has been identified as the main driving force for budding. Both LCMV and Lassa virus Z proteins bud from cells in the absence of other viral proteins as enveloped virus-like particles. Z accumulates near the inner surface of the plasma membrane where budding takes place. Furthermore, biochemical data have shown that Z is strongly membrane associated. The primary sequence of Z lacks a typical transmembrane domain and until now it is not understood by which mechanism Z is able to interact with cellular membranes. In this report, we analyzed the role of N-terminal myristoylation for the membrane binding of Lassa virus Z. We show that disruption of the N-terminal myristoylation signal by substituting the N-terminal glycine with alanine (Z-G2A mutant) resulted in a significant reduction of Z protein association with cellular membranes. Furthermore, removal of the myristoylation site resulted in a relocalization of Z from a punctuate distribution to a more diffuse cellular distribution pattern. Finally, treatment of Lassa virus-infected cells with various myristoylation inhibitors drastically reduced efficient Lassa virus replication. Our data indicate that myristoylation of Z is critical for its binding ability to lipid membranes and thus, for effective virus budding.