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Journal of Virology, September 2000, p. 8692-8699, Vol. 74, No. 18
Department of Microbiology and Immunology,
The Pennsylvania State University College of Medicine, Hershey,
Pennsylvania 17033
Received 8 December 1999/Accepted 26 June 2000
The retroviral Gag protein is capable of directing the production
and release of virus-like particles in the absence of all other viral
components. Budding normally occurs after Gag is transported to the
plasma membrane by its membrane-targeting and -binding (M)
domain. In the Rous sarcoma virus (RSV) Gag protein, the M domain is
contained within the first 86 amino acids. When M is deleted, membrane
association and budding fail to occur. Budding is restored when M is
replaced with foreign membrane-binding sequences, such as that of the
Src oncoprotein. Moreover, the RSV M domain is capable of targeting
heterologous proteins to the plasma membrane. Although the solution
structure of the RSV M domain has been determined, the mechanism by
which M specifically targets Gag to the plasma membrane rather than to
one or more of the large number of internal membrane surfaces (e.g.,
the Golgi apparatus, endoplasmic reticulum, and nuclear, mitochondrial,
or lysosomal membranes) is unknown. To further investigate the
requirements for targeting proteins to discrete cellular
locations, we have replaced the M domain of RSV with the product of the
unique long region 11 (UL11) gene of herpes simplex virus
type 1. This 96-amino-acid myristylated protein is thought to be
involved in virion transport and envelopment at internal membrane
sites. When the first 100 amino acids of RSV Gag (including the M
domain) were replaced by the entire UL11 sequence, the chimeric protein
localized at and budded into the Golgi apparatus rather than being
targeted to the plasma membrane. Myristate was found to be required for
this specific targeting, as were the first 49 amino acids of UL11,
which contain an acidic cluster motif. In addition to shedding new
light on UL11, these experiments demonstrate that RSV Gag can be
directed to internal cellular membranes and suggest that regions
outside of the M domain do not contain a dominant plasma
membrane-targeting motif.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Membrane Targeting Properties of a Herpesvirus
Tegument Protein-Retrovirus Gag Chimera

*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Dr., P.O. Box 850, Hershey, PA 17033. Phone:
(717) 531-3528. Fax: (717) 531-6522. E-mail: jwills{at}psu.edu.
Present address: Infectious Diseases Section, Wyeth Ayerst
Research, Pearl River, NY 10965.
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