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

• Type of Material: Article
• Authors: Lynsey N. Crosby, Emory University; Anita McCormick, Emory University; Edward Mocarski, Emory University
• Language: English
• Date: 2013-02-20
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Open Archive. © 2012 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virol.2012.12.002
• Title of Journal or Parent Work: Virology
• ISSN: 0042-6822
• Volume: 436
• Issue: 2
• Start Page: 274
• End Page: 283
• Grant/Funding Information: This work was supported by PHS grants RO1 AI020211 and AI030363.
• Keywords: Life Sciences & Biomedicine; RECOGNITION; MITOCHONDRIAL MORPHOGENESIS; Mitochondria; DISSEMINATION; PROTEIN; VIRUS; BAX; Herpesvirus; CHEMOKINE HOMOLOG; Macrophage; CELL ACTIVATION RECEPTOR; MEDIATED APOPTOSIS; Apoptosis; Virology; DEATH; Science & Technology
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

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.