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Journal of Virology, November 2000, p. 9818-9827, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Mutations in the PPPY Motif of Vesicular Stomatitis Virus Matrix Protein Reduce Virus Budding by Inhibiting a Late Step in Virion Release

Himangi R. Jayakar,1 K. Gopal Murti,2 and Michael A. Whitt1,*

Department of Microbiology and Immunology, University of Tennessee---Memphis, Memphis, Tennessee 38163,1 and Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 381012

Received 8 May 2000/Accepted 25 July 2000

The N terminus of the matrix (M) protein of vesicular stomatitis virus (VSV) and of other rhabdoviruses contains a highly conserved PPPY sequence (or PY motif) similar to the late (L) domains in the Gag proteins of some retroviruses. These L domains in retroviral Gag proteins are required for efficient release of virus particles. In this report, we show that mutations in the PPPY sequence of the VSV M protein reduce virus yield by blocking a late stage in virus budding. We also observed a delay in the ability of mutant viruses to cause inhibition of host gene expression compared to wild-type (WT) VSV. The effect of PY mutations on virus budding appears to be due to a block at a stage just prior to virion release, since electron microscopic examination of PPPA mutant-infected cells showed a large number of assembled virions at the plasma membrane trapped in the process of budding. Deletion of the glycoprotein (G) in addition to these mutations further reduced the virus yield to less than 1% of WT levels, and very few particles were assembled at the cell surface. This observation suggested that G protein aids in the initial stage of budding, presumably during the formation of the bud site. Overall, our results confirm that the PPPY sequence of the VSV M protein possesses L domain activity analogous to that of the retroviral Gag proteins.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Medicine, University of Tennessee---Memphis, 858 Madison Ave., Memphis, TN 38163. Phone: (901) 448-4634. Fax: (901) 448-8462. E-mail: mwhitt{at}utmem.edu.

Journal of Virology, November 2000, p. 9818-9827, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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