title: Non-redundant and redundant roles of cytomegalovirus gH/gL complexes in host organ entry and intra-tissue spread.
abstract: Herpesviruses form different gH/gL virion envelope glycoprotein complexes that serve as entry complexes for mediating viral cell-type tropism in vitro; their roles in vivo, however, remained speculative and can be addressed experimentally only in animal models. For murine cytomegalovirus two alternative gH/gL complexes, gH/gL/gO and gH/gL/MCK-2, have been identified. A limitation of studies on viral tropism in vivo has been the difficulty in distinguishing between infection initiation by viral entry into first-hit target cells and subsequent cell-to-cell spread within tissues. As a new strategy to dissect these two events, we used a gO-transcomplemented ΔgO mutant for providing the gH/gL/gO complex selectively for the initial entry step, while progeny virions lack gO in subsequent rounds of infection. Whereas gH/gL/gO proved to be critical for establishing infection by efficient entry into diverse cell types, including liver macrophages, endothelial cells, and hepatocytes, it was dispensable for intra-tissue spread. Notably, the salivary glands, the source of virus for host-to-host transmission, represent an exception in that entry into virus-producing cells did not strictly depend on either the gH/gL/gO or the gH/gL/MCK-2 complex. Only if both complexes were absent in gO and MCK-2 double-knockout virus, in vivo infection was abolished at all sites.
authors: Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors: Niels A W
authors: NA
authors: Lemmermann
authors: School of Medicine, University of Rijeka, Rijeka, Croatia.
authors: Astrid
authors: A
authors: Krmpotic
authors: Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors: Jürgen
authors: J
authors: Podlech
authors: School of Medicine, University of Rijeka, Rijeka, Croatia; Max von Pettenkofer-Institute for Virology, Ludwig-Maximilians-University Munich, Munich, Germany.
authors: Ilija
authors: I
authors: Brizic
authors: Max von Pettenkofer-Institute for Virology, Ludwig-Maximilians-University Munich, Munich, Germany.
authors: Adrian
authors: A
authors: Prager
authors: Research Unit Gene Vectors, Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), Munich, Germany.
authors: Heiko
authors: H
authors: Adler
authors: Institute for Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors: Astrid
authors: A
authors: Karbach
authors: Max von Pettenkofer-Institute for Virology, Ludwig-Maximilians-University Munich, Munich, Germany.
authors: Yiquan
authors: Y
authors: Wu
authors: School of Medicine, University of Rijeka, Rijeka, Croatia.
authors: Stipan
authors: S
authors: Jonjic
authors: Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors: Matthias J
authors: MJ
authors: Reddehase
authors: Max von Pettenkofer-Institute for Virology, Ludwig-Maximilians-University Munich, Munich, Germany.
authors: Barbara
authors: B
authors: Adler
mesh_terms: D000818:Animals; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000378:metabolism / Q000635:transmission*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D014759:Viral Envelope Proteins / Q000378:metabolism*; D056189:Viral Tropism / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C071440:glycoprotein H, Cytomegalovirus; C439068:glycoprotein O, cytomegalovirus