title: Gene products of the embedded m41/m41.1 locus of murine cytomegalovirus differentially influence replication and pathogenesis.
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.
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Lynsey N
authors.initials: LN
authors.lastname: Crosby
authors.forename: A Louise
authors.initials: AL
authors.lastname: McCormick
authors.forename: Edward S
authors.initials: ES
authors.lastname: Mocarski
mesh_terms: D000595:Amino Acid Sequence; D000825:Animal Structures / Q000821:virology; D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000473:pathology* / Q000821:virology; D008264:Macrophages / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D014764:Viral Proteins; D037521:Virulence Factors