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Wagner, F.M.* ; Brizic, I.* ; Prager, A.* ; Trsan, T.* ; Arapovic, M.* ; Lemmermann, N.A.W.* ; Podlech, J.* ; Reddehase, M.J.* ; Lemnitzer, F.* ; Bosse, J.B.* ; Gimpfl, M.* ; Marcinowski, L.* ; MacDonald, M.* ; Adler, H. ; Koszinowski, U.H.* ; Adler, B.*

The viral chemokine MCK-2 of murine cytomegalovirus promotes infection as part of a gH/gL/MCK-2 complex.

PLoS Pathog. 9:e1003493 (2013)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Epithelial-cell Tropism ; Endothelial-cells ; Rhesus Cytomegalovirus ; Salivary-glands ; Virus Entry ; Antigen Presentation ; Crystal-structure ; Ul131-128 Genes ; Beta Chemokine ; Class-ii
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 1553-7366
e-ISSN 1553-7374
Journal PLoS Pathogens
Quellenangaben Volume: 9, Issue: 7, Pages: , Article Number: e1003493 Supplement: ,
Publisher Public Library of Science (PLoS)
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-501500-006
DOI 10.1371/journal.ppat.1003493
WOS ID WOS:000322316700036
Scopus ID 84884802324
Erfassungsdatum 2013-07-30
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