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Journal of Virology, March 2007, p. 2573-2583, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.02454-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The IE2 60-Kilodalton and 40-Kilodalton Proteins Are Dispensable for Human Cytomegalovirus Replication but Are Required for Efficient Delayed Early and Late Gene Expression and Production of Infectious Virus{triangledown}

Elizabeth A. White,1 Christia J. Del Rosario,1 Rebecca L. Sanders,1 and Deborah H. Spector2*

Division of Biological Sciences,1 Department of Cellular and Molecular Medicine, Center for Molecular Genetics, and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093-07122

Received 7 November 2006/ Accepted 24 December 2006

The human cytomegalovirus (HCMV) IE2 86-kDa protein is an essential transactivator of viral and cellular gene expression. Additional proteins of 60 and 40 kDa are expressed from the IE2 gene at late times postinfection and are identical to the C terminus of IE2 86. We have constructed HCMV recombinants that express wild-type full-length IE2 86 but do not express the IE2 40- and 60-kDa proteins. Each of these recombinants is viable, indicating that neither the 60-kDa nor the 40-kDa protein is required for virus replication, either alone or in combination. Cells infected with the IE2 60 and IE2 40 deletion mutants, however, exhibit decreased expression of selected viral genes at late times. In particular, expression of the viral DNA replication factor UL84 is affected by the deletion of IE2 40, and expression of the tegument protein pp65 (ppUL83) is affected by the deletion of both IE2 40 and IE2 60. IE2 60 and IE2 40 are also required for the production of normal levels of infectious virus. Finally, IE2 40 appears to function as a repressor of major immediate-early transcription in the infected cell. These results begin to define functions for the IE2 60- and IE2 40-kDa proteins and indicate that these products contribute both to the expression of selected viral genes and to the overall progression of the infection.

* Corresponding author. Mailing address: Cellular and Molecular Medicine, 9500 Gilman Dr., La Jolla, CA 92093. Phone: (858) 534-4584. Fax: (858) 534-6083. E-mail: dspector{at}ucsd.edu.

{triangledown} Published ahead of print on 3 January 2007.

Journal of Virology, March 2007, p. 2573-2583, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.02454-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sanders, R. L., Del Rosario, C. J., White, E. A., Spector, D. H. (2008). Internal Deletions of IE2 86 and Loss of the Late IE2 60 and IE2 40 Proteins Encoded by Human Cytomegalovirus Affect the Levels of UL84 Protein but Not the Amount of UL84 mRNA or the Loading and Distribution of the mRNA on Polysomes. J. Virol. 82: 11383-11397 [Abstract] [Full Text]  
  • Sanders, R. L., Clark, C. L., Morello, C. S., Spector, D. H. (2008). Development of Cell Lines That Provide Tightly Controlled Temporal Translation of the Human Cytomegalovirus IE2 Proteins for Complementation and Functional Analyses of Growth-Impaired and Nonviable IE2 Mutant Viruses. J. Virol. 82: 7059-7077 [Abstract] [Full Text]  
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