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Journal of Virology, March 2005, p. 3525-3535, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3525-3535.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Complex Formation among Murine Cytomegalovirus US22 Proteins Encoded by Genes M139, M140, and M141

Zaruhi Karabekian ,1,{dagger},{ddagger} Laura K. Hanson,1,{dagger} Jacquelyn S. Slater,1 Neel K. Krishna,2 Lisa L. Bolin,1 Julie A. Kerry,1 and Ann E. Campbell1*

Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School,1 Department of Pediatrics and The Center for Pediatric Research, Eastern Virginia Medical School and Children's Hospital of The King's Daughters, Norfolk, Virginia2

Received 20 October 2003/ Accepted 26 October 2004

The murine cytomegalovirus (MCMV) proteins encoded by US22 genes M139, M140, and M141 function, at least in part, to regulate replication of this virus in macrophages. Mutant MCMV having one or more of these genes deleted replicates poorly in macrophages in culture and in the macrophage-dense environment of the spleen. In this report, we demonstrate the existence of stable complexes formed by the products of all three of these US22 genes, as well as a complex composed of the products of M140 and M141. These complexes form in the absence of other viral proteins; however, the pM140/pM141 complex serves as a requisite binding partner for the M139 gene products. Products from all three genes colocalize to a perinuclear region of the cell juxtaposed to or within the cis-Golgi region but excluded from the trans-Golgi region. Interestingly, expression of pM141 redirects pM140 from its predominantly nuclear residence to the perinuclear, cytoplasmic locale where these US22 proteins apparently exist in complex. Thus, complexing of these nonessential, early MCMV proteins likely confers a function(s) independent of each individual protein and important for optimal replication of MCMV in its natural host.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 W. Olney Rd., Norfolk, VA 23507. Phone: (757) 446-5667. Fax: (757) 624-2255. E-mail: campbeae{at}evms.edu.

{dagger} Z.K. and L.K.H. contributed equally to this work.

{ddagger} Present address: TolerGenics, Inc., Rockville, MD 20850.

Journal of Virology, March 2005, p. 3525-3535, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3525-3535.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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