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Journal of Virology, November 2003, p. 11633-11643, Vol. 77, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.21.11633-11643.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Murine Cytomegalovirus m41 Open Reading Frame Encodes a Golgi-Localized Antiapoptotic Protein

Wolfram Brune,1,2* Michael Nevels,1 and Thomas Shenk1

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544,1 Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, D-97078 Würzburg, Germany2

Received 5 May 2003/ Accepted 24 July 2003

Viruses have evolved various strategies to prevent premature apoptosis of infected host cells. Some of the viral genes mediating antiapoptotic functions have been identified by their homology to cellular genes, but others are structurally unrelated to genes of known function. In this study, we used a random, unbiased approach to identify such genes in the murine cytomegalovirus genome. From a library of random transposon insertion mutants, a mutant virus that caused premature cell death was isolated. The transposon was inserted within open reading frame m41. An independently constructed m41 deletion mutant showed the same phenotype, whereas deletion mutants lacking the adjacent genes m40 and M42 did not. Apoptosis occurred in different cell types, could be blocked by caspase inhibitors, and did not require p53. Within the murine cytomegalovirus genome, m41, m40, and m39 form a small cluster of genes of unknown function. They are homologous to r41, r40, and r39 of rat cytomegalovirus, but lack sequence homology to UL41, UL40, and UL37 exon 1 (UL37x1) which are located at the corresponding positions of the human cytomegalovirus genome. Unlike UL37x1 of human cytomegalovirus, which encodes a mitochondrion-localized inhibitor of apoptosis that is essential for virus replication, m41 encodes a protein that localizes to the Golgi apparatus. The murine cytomegalovirus m41 product is the first example of a Golgi-localized protein that prevents premature apoptosis and thus extends the life span of infected cells.

* Corresponding author. Mailing address: Rudolf Virchow Zentrum für Experimentelle Biomedizin, Universität Würzburg, Versbacher Str. 9, D-97078 Würzburg, Germany. Phone: 49 931 20148903. Fax: 49 931 20148123. E-mail: wolfram.brune{at}virchow.uni-wuerzburg.de.

Journal of Virology, November 2003, p. 11633-11643, Vol. 77, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.21.11633-11643.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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