Non-redundant and Redundant Roles of Cytomegalovirus gH/gL Complexes in Host Organ Entry and Intra-tissue Spread

PLoS Pathogens

Yiquan Wu¹  Niels A. W. Lemmermann²  Barbara Adler²  Jürgen Podlech²  Adrian Prager³  Stipan Jonjic³  Heiko Adler³  Astrid Karbach⁴  Astrid Krmpotic⁵  Ilija Brizic⁵  Matthias J. Reddehase⁵ 

[1] Institute for Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany;Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany;Max von Pettenkofer-Institute for Virology, Ludwig-Maximilians-University Munich, Munich, Germany;Research Unit Gene Vectors, Helmholtz Zentrum München—German Research Center for Environmental Health (GmbH), Munich, Germany;School of Medicine, University of Rijeka, Rijeka, Croatia

关键词: Virions;    Viral entry;    Cell cultures;    Cell staining;    Epithelial cells;    Fibroblasts;    Antibodies;    Human cytomegalovirus;   

DOI  :  10.1371/journal.ppat.1004640

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY