Type I Interferons Direct Gammaherpesvirus Host Colonization
AuthorTan, CSE; Lawler, C; May, JS; Belz, GT; Stevenson, PG
Source TitlePLoS Pathogens
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sBelz, Gabrielle
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsTan, C. S. E., Lawler, C., May, J. S., Belz, G. T. & Stevenson, P. G. (2016). Type I Interferons Direct Gammaherpesvirus Host Colonization. PLOS PATHOGENS, 12 (5), https://doi.org/10.1371/journal.ppat.1005654.
Access StatusOpen Access
Gamma-herpesviruses colonise lymphocytes. Murid Herpesvirus-4 (MuHV-4) infects B cells via epithelial to myeloid to lymphoid transfer. This indirect route entails exposure to host defences, and type I interferons (IFN-I) limit infection while viral evasion promotes it. To understand how IFN-I and its evasion both control infection outcomes, we used Mx1-cre mice to tag floxed viral genomes in IFN-I responding cells. Epithelial-derived MuHV-4 showed low IFN-I exposure, and neither disrupting viral evasion nor blocking IFN-I signalling markedly affected acute viral replication in the lungs. Maximising IFN-I induction with poly(I:C) increased virus tagging in lung macrophages, but the tagged virus spread poorly. Lymphoid-derived MuHV-4 showed contrastingly high IFN-I exposure. This occurred mainly in B cells. IFN-I induction increased tagging without reducing viral loads; disrupting viral evasion caused marked attenuation; and blocking IFN-I signalling opened up new lytic spread between macrophages. Thus, the impact of IFN-I on viral replication was strongly cell type-dependent: epithelial infection induced little response; IFN-I largely suppressed macrophage infection; and viral evasion allowed passage through B cells despite IFN-I responses. As a result, IFN-I and its evasion promoted a switch in infection from acutely lytic in myeloid cells to chronically latent in B cells. Murine cytomegalovirus also showed a capacity to pass through IFN-I-responding cells, arguing that this is a core feature of herpesvirus host colonization.
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