Type I Interferons Direct Gammaherpesvirus Host Colonization

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. © 2016 tan et al.