title: Equine herpesvirus type 1 replication is delayed in CD172a+ monocytic cells and controlled by histone deacetylases.
abstract: Equine herpesvirus type 1 (EHV-1) replicates in the epithelial cells of the upper respiratory tract and disseminates through the body via a cell-associated viraemia in monocytic cells, despite the presence of neutralizing antibodies. However, the mechanism by which EHV-1 hijacks immune cells and uses them as 'Trojan horses' in order to disseminate inside its host is still unclear. Here, we hypothesize that EHV-1 delays its replication in monocytic cells in order to avoid recognition by the immune system. We compared replication kinetics in vitro of EHV-1 in RK-13, a cell line fully susceptible to EHV-1 infection, and primary horse cells from the myeloid lineage (CD172a(+)). We found that EHV-1 replication was restricted to 4 % of CD172a(+) cells compared with 100 % in RK-13 cells. In susceptible CD172a(+) cells, the expression of immediate-early (IEP) and early (EICP22) proteins was delayed in the cell nuclei by 2-3 h post-infection (p.i.) compared with RK-13, and the formation of replicative compartments by 15 h p.i. Virus production in CD172a(+) cells was significantly lower (from 10(1.7) to 10(3.1) TCID50 per 10(5) inoculated cells) than in RK-13 (from 10(5) to 10(5.7) TCID50 per 10(5) inoculated cells). Less than 0.02 % of inoculated CD172a(+) cells produced and transmitted infectious virus to neighbouring cells. Pre-treatment of CD172a(+) cells with inhibitors of histone deacetylase activity increased and accelerated viral protein expression at very early times of infection and induced productive infection in CD172a(+) cells. Our results demonstrated that the restriction and delay of EHV-1 replication in CD172a(+) cells are part of an immune evasive strategy and involve silencing of EHV-1 gene expression associated with histone deacetylases.
authors.affiliation: Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medecine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
authors.forename: Kathlyn
authors.initials: K
authors.lastname: Laval
authors.affiliation: Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medecine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
authors.forename: Herman W
authors.initials: HW
authors.lastname: Favoreel
authors.affiliation: Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medecine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nauwynck
mesh_terms: D000818:Animals; D002460:Cell Line; D004261:DNA Replication / Q000235:genetics*; D006566:Herpesviridae Infections / Q000378:metabolism* / Q000821:virology; D004861:Herpesvirus 1, Equid / Q000235:genetics*; D006655:Histone Deacetylases / Q000378:metabolism*; D006734:Horse Diseases / Q000378:metabolism* / Q000821:virology; D006736:Horses; D009000:Monocytes / Q000378:metabolism* / Q000821:virology; D011971:Receptors, Immunologic / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication / Q000235:genetics*
chemical_list: D011971:Receptors, Immunologic; D014764:Viral Proteins; D006655:Histone Deacetylases