1887

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 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 to 10 TCID per 10 inoculated cells) than in RK-13 (from 10 to 10 TCID per 10 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.

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2015-01-01
2021-07-24
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