Equine herpesvirus type 1 replication is delayed in CD172a+ monocytic cells and controlled by histone deacetylases Laval, Kathlyn and Favoreel, Herman W. and Nauwynck, Hans J.,, 96, 118-130 (2015), doi = https://doi.org/10.1099/vir.0.067363-0, publicationName = Microbiology Society, issn = 0022-1317, 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 101.7 to 103.1 TCID50 per 105 inoculated cells) than in RK-13 (from 105 to 105.7 TCID50 per 105 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., language=, type=