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Journal of Virology, January 2009, p. 262-272, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01827-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Transactivator IE1 Is Required for Baculovirus Early Replication Events That Trigger Apoptosis in Permissive and Nonpermissive Cells{triangledown}

Kimberly L. W. Schultz,1,{dagger} Justin A. Wetter,1,{dagger},{ddagger} Diccon C. Fiore,1 and Paul D. Friesen1,2*

Institute for Molecular Virology, Department of Biochemistry,2 Cellular and Molecular Biology Program, Graduate School and College of Agricultural and Life Sciences; University of Wisconsin—Madison, Madison, Wisconsin 537061

Received 29 August 2008/ Accepted 14 October 2008

Immediate early viral protein IE1 is a potent transcriptional activator encoded by baculoviruses. Although the requirement of IE1 for multiplication of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) is well established, the functional roles of IE1 during infection are unclear. Here, we used RNA interference to ablate IE1, plus its splice variant IE0, and thereby define in vivo activities of these early proteins, including gene-specific regulation and induction of host cell apoptosis. Confirming an essential replicative role, simultaneous ablation of IE1 and IE0 by gene-specific double-stranded RNAs inhibited AcMNPV late gene expression, reduced yields of budded virus by more than 1,000-fold, and blocked production of occluded virus particles. Depletion of IE1 and IE0 had no effect on early expression of the envelope fusion protein gene gp64 but abolished early expression of the caspase inhibitor gene p35, which is required for prevention of virus-induced apoptosis. Thus, IE1 is a positive, gene-specific transactivator. Whereas an AcMNPV p35 deletion mutant caused widespread apoptosis in permissive Spodoptera frugiperda cells, ablation of IE1 and IE0 prevented this apoptosis. Silencing of ie-1 also prevented AcMNPV-induced apoptosis in nonpermissive Drosophila melanogaster cells. Thus, de novo synthesis of IE1 is required for virus-induced apoptosis. We concluded that IE1 causes apoptosis directly or contributes indirectly by promoting virus replication events that subsequently trigger cell death. This study reveals that IE1 is a gene-selective transcriptional activator which is required not only for expedition of virus multiplication but also for blocking of its own proapoptotic activity by upregulation of baculovirus apoptotic suppressors.

* Corresponding author. Mailing address: Institute for Molecular Virology, R. M. Bock Laboratories, University of Wisconsin—Madison, 1525 Linden Dr., Madison, WI 53706-1596. Phone: (608) 262-7774. Fax: (608) 262-7414. E-mail: pfriesen{at}wisc.edu

{triangledown} Published ahead of print on 22 October 2008.

{dagger} These two authors contributed equally.

{ddagger} Present address: Invitrogen, 501 Charmany Drive, Madison, WI 53706.

Journal of Virology, January 2009, p. 262-272, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01827-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Schultz, K. L. W., Friesen, P. D. (2009). Baculovirus DNA Replication-Specific Expression Factors Trigger Apoptosis and Shutoff of Host Protein Synthesis during Infection. J. Virol. 83: 11123-11132 [Abstract] [Full Text]  


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