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Journal of Virology, October 2004, p. 11443-11448, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11443-11448.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Myristoylation of the RING Finger Z Protein Is Essential for Arenavirus Budding

Mar Perez, Dori L. Greenwald, and Juan Carlos de La Torre*

Department of Neuropharmacology, Division of Virology, The Scripps Research Institute, La Jolla, California

Received 21 April 2004/ Accepted 15 June 2004

The arenavirus small RING finger Z protein is the main driving force of arenavirus budding. The primary structure of Z is devoid of hydrophobic transmembrane domains, but both lymphocytic choriomeningitis virus (LCMV) and Lassa fever virus Z proteins accumulate near the inner surface of the plasma membrane and are strongly membrane associated. All known arenavirus Z proteins contain a glycine (G) at position 2, which is a potential acceptor site for a myristoyl moiety. Metabolic labeling showed incorporation of [3H]myristic acid by wild-type Z protein but not by the G2A mutant. The mutation G2A eliminated Z-mediated budding. Likewise, treatment with the myristoylation inhibitor 2-hydroxymyristic acid inhibited Z-mediated budding, eliminated formation of virus-like particles, and caused a dramatic reduction in virus production in LCMV-infected cells. Budding activity was restored in G2A mutant Z proteins by the addition of the myristoylation domain of the tyrosine protein kinase Src to their N termini. These findings indicate N-terminal myristoylation of Z plays a key role in arenavirus budding.

* Corresponding author. Mailing address: The Scripps Research Institute, IMM6, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-9462. Fax: (858) 784-9981. E-mail: juanct{at}scripps.edu.

Journal of Virology, October 2004, p. 11443-11448, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11443-11448.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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