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)
    
    
    
      
      
	
	    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
    
 
    
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        Keywords
        Epstein-barr-virus; To-cell Spread; Murine Cytomegalovirus; Epithelial-cells; Endothelial-cells; Chemokine Homolog; Virion Envelope; Ul131-128 Genes; Salivary-glands; Bone-marrow
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2015
    
 
    
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        HGF-reported in Year
        2015
    
 
    
    
        ISSN (print) / ISBN
        1553-7366
    
 
    
        e-ISSN
        1553-7374
    
 
    
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	    Volume: 11,  
	    Issue: 2,  
	    Pages: ,  
	    Article Number: e1004640 
	    Supplement: ,  
	
    
 
    
        
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            Publisher
            Public Library of Science (PLoS)
        
 
        
            Publishing Place
            San Francisco
        
 
	
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30203 - Molecular Targets and Therapies
    
 
    
        Research field(s)
        Immune Response and Infection
    
 
    
        PSP Element(s)
        G-501500-006
    
 
    
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        Erfassungsdatum
        2015-02-08