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

Lemmermann NAW, Krmpotic A, Podlech J, Brizic I, Prager A, Adler H, Karbach A, Wu Y, Jonjic S, Reddehase MJ, Adler B (2015)

Publication Type: Journal article

Publication year: 2015

Journal

PLoS Pathogens Public Library of Science

Book Volume: 11

Pages Range: e1004640

Journal Issue: 2

DOI: 10.1371/journal.ppat.1004640

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 ?gO 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 with CRIS profile

Astrid Karbach Institute of Clinical and Molecular Virology

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE) Sveučilište u Rijeci / University of Rijeka HR Croatia (HR)

How to cite

APA:

Lemmermann, N.A.W., Krmpotic, A., Podlech, J., Brizic, I., Prager, A., Adler, H.,... Adler, B. (2015). Non-redundant and redundant roles of cytomegalovirus gH/gL complexes in host organ entry and intra-tissue spread. PLoS Pathogens, 11(2), e1004640. https://doi.org/10.1371/journal.ppat.1004640

MLA:

Lemmermann, Niels A. W., et al. "Non-redundant and redundant roles of cytomegalovirus gH/gL complexes in host organ entry and intra-tissue spread." PLoS Pathogens 11.2 (2015): e1004640.

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