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Author Notes:

Corresponding author. Fax: þ1 404 712 9736. E-mail addresses: mocarski@emory.edu, mocarski@stanford.edu (E.S. Mocarski).

We thank Linda Roback for technical assistance, Doug Green for providing knockout mice, Chris Andoniou and Mariapia Degli-Esposti for discussions and for materials provided, and the Mocarski lab members for their critical feedback on the manuscript.

Subjects:

Research Funding:

This work was supported by PHS grants RO1 AI020211 and AI030363.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Virology
  • Herpesvirus
  • Apoptosis
  • Mitochondria
  • Macrophage
  • CELL ACTIVATION RECEPTOR
  • MITOCHONDRIAL MORPHOGENESIS
  • MEDIATED APOPTOSIS
  • CHEMOKINE HOMOLOG
  • BAX
  • DEATH
  • VIRUS
  • PROTEIN
  • DISSEMINATION
  • RECOGNITION

Gene products of the embedded m41/m41.1 locus of murine cytomegalovirus differentially influence replication and pathogenesis

Tools:

Journal Title:

Virology

Volume:

Volume 436, Number 2

Publisher:

, Pages 274-283

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Cytomegaloviruses utilize overlapping and embedded reading frames as a way to efficiently package and express all genes necessary to carry out a complex lifecycle. Murine cytomegalovirus encodes a mitochondrial-localized inhibitor of Bak oligomerization (vIBO) from m41.1, a reading frame that is embedded within the m41 gene. The m41.1-encoded mitochondrial protein and m41-encoded Golgi-localized protein have both been implicated in cell death suppression; however, their contribution to viral infection within the host has not been investigated. Here, we report that mitochondrial-localized m41.1 (vIBO) is required for optimal viral replication in macrophages and has a modest impact on dissemination in infected mice. In contrast, Golgi-localized m41 protein is dispensable during acute infection and dissemination as well as for latency. All together, these data indicate that the primary evolutionary focus of this locus is to maintain mitochondrial function through inhibition of Bak-mediated death pathways in support of viral pathogenesis. © 2012 Elsevier Inc.

Copyright information:

Open Archive. © 2012 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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