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Lemmermann, N.A.W.* ; Krmpotic, A.* ; Podlech, J.* ; Brizic, I.* ; Prager, A.* ; Adler, H. ; Karbach, A.* ; Wu, Y.* ; Jonjic, S.* ; Reddehase, M.J.* ; Adler, B.*

Non-redundant and redundant roles of cytomegalovirus gH/gL complexes in host organ entry and intra-tissue spread.

PLoS Pathog. 11:e1004640 (2015)

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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Epstein-barr-virus; To-cell Spread; Murine Cytomegalovirus; Epithelial-cells; Endothelial-cells; Chemokine Homolog; Virion Envelope; Ul131-128 Genes; Salivary-glands; Bone-marrow

ISSN (print) / ISBN 1553-7366

e-ISSN 1553-7374

Journal PLoS Pathogens

Quellenangaben Volume: 11, Issue: 2, Article Number: e1004640

Publisher Public Library of Science (PLoS)

Publishing Place San Francisco

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Gene Vector (AGV)