The Viral Chemokine MCK-2 of Murine Cytomegalovirus Promotes Infection as Part of a gH/gL/MCK-2 Complex

PLoS Pathogens

Tihana Trsan¹  Maja Arapovic¹  Niels A. W. Lemmermann²  Matthias J. Reddehase²  Jürgen Podlech²  Margaret MacDonald³  Adrian Prager⁴  Lisa Marcinowski⁴  Jens Bernhard Bosse⁴  Felicia M. Wagner⁴  Barbara Adler⁴  Ulrich H. Koszinowski⁴  Ilija Brizic⁴  Frederic Lemnitzer⁴  Martina Gimpfl⁴  Heiko Adler⁵ 

[1] Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia;Institute for Virology and Research Center for Immunology (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany;Laboratory of Virology and Infectious Disease, Rockefeller University, New York, New York, United States of America;Max von Pettenkofer-Institute for Virology, Ludwig-Maximilians-University Munich, Munich, Germany;Research Unit Gene Vectors, German Research Center for Environmental Health (GmbH), Munich, Germany

关键词: Macrophages;    Antibodies;    Immunoprecipitation;    Cell staining;    Chemokines;    Salivary gl;    s;    Fibroblasts;    Human cytomegalovirus;   

DOI  :  10.1371/journal.ppat.1003493

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Human cytomegalovirus (HCMV) forms two gH/gL glycoprotein complexes, gH/gL/gO and gH/gL/pUL(128,130,131A), which determine the tropism, the entry pathways and the mode of spread of the virus. For murine cytomegalovirus (MCMV), which serves as a model for HCMV, a gH/gL/gO complex functionally homologous to the HCMV gH/gL/gO complex has been described. Knock-out of MCMV gO does impair, but not abolish, virus spread indicating that also MCMV might form an alternative gH/gL complex. Here, we show that the MCMV CC chemokine MCK-2 forms a complex with the glycoprotein gH, a complex which is incorporated into the virion. We could additionally show that mutants lacking both, gO and MCK-2 are not able to produce infectious virus. Trans-complementation of these double mutants with either gO or MCK-2 showed that both proteins can promote infection of host cells, although through different entry pathways. MCK-2 has been extensively studied in vivo by others. It has been shown to be involved in attracting cells for virus dissemination and in regulating antiviral host responses. We now show that MCK-2, by forming a complex with gH, strongly promotes infection of macrophages in vitro and in vivo. Thus, MCK-2 may play a dual role in MCMV infection, as a chemokine regulating the host response and attracting specific target cells and as part of a glycoprotein complex promoting entry into cells crucial for virus dissemination.

【 授权许可】

CC BY