title: Luciferase-tagged wild-type and tropism-deficient mouse cytomegaloviruses reveal early dynamics of host colonization following peripheral challenge.
abstract: Cytomegaloviruses (CMVs) establish persistent, systemic infections and cause disease by maternal-foetal transfer, suggesting that their dissemination is a key target for antiviral intervention. Late clinical presentation has meant that human CMV (HCMV) dissemination is not well understood. Murine CMV (MCMV) provides a tractable model. Whole mouse imaging of virus-expressed luciferase has proved a useful way to track systemic infections. MCMV, in which the abundant lytic gene M78 was luciferase-tagged via a self-cleaving peptide (M78-LUC), allowed serial, unbiased imaging of systemic and peripheral infection without significant virus attenuation. Ex vivo luciferase imaging showed greater sensitivity than plaque assay, and revealed both well-known infection sites (the lungs, lymph nodes, salivary glands, liver, spleen and pancreas) and less explored sites (the bone marrow and upper respiratory tract). We applied luciferase imaging to tracking MCMV lacking M33, a chemokine receptor conserved in HCMV and a proposed anti-viral drug target. M33-deficient M78-LUC colonized normally in peripheral sites and local draining lymph nodes but spread poorly to the salivary gland, suggesting a defect in vascular transport consistent with properties of a chemokine receptor.
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Farrell
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.|Child Health Research Centre, University of Queensland, South Brisbane, Australia.
authors.forename: Martha
authors.initials: M
authors.lastname: Oliveira
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.
authors.forename: Kate
authors.initials: K
authors.lastname: Macdonald
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.
authors.forename: Joseph
authors.initials: J
authors.lastname: Yunis
authors.affiliation: Institut fur Klinische und Molekulare Virologie, Friedrich-Alexander-Universitat Erlangen-Nurnber, Erlangen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Mach
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Bruce
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Stevenson
authors.affiliation: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Cardin
authors.affiliation: Child Health Research Centre, University of Queensland, South Brisbane, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Davis-Poynter
mesh_terms: D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000821:virology*; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D056189:Viral Tropism
chemical_list: D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D008156:Luciferases