Differential innate immune response of endometrial cells to porcine reproductive and respiratory syndrome virus type 1 versus type 2

Modification of cellular and immunological events due to porcine reproductive and respiratory syndrome virus (PRRSV) infection is associated with pathogenesis in lungs. PRRSV also causes female reproductive dysfunction and persistent infection which can spread to fetus, stillbirth, and offspring. In this study, alterations in cellular and innate immune responses to PRRSV type 1 or type 2 infection, including expression of PRRSV mediators, mRNA expression of toll-like receptor (TLRs) and cytokine, and cytokine secretion, were examined in primary porcine glandular endometrial cells (PGE). Cell infectivity as observed by cytopathic effect (CPE), PRRSV nucleocapsid proteins, and viral nucleic acids was early detected at two days post-infection (2 dpi) and persisted to 6 dpi. Higher percentage of CPE and PRRSV positive cells were detected in type 2 infection. PRRSV mediator proteins, CD151, CD163, sialoadhesin (Sn), integrin and vimentin, were upregulated following type 1 and type 2 infection. CD151, CD163 and Sn were upregulated by type 2. Both PRRSV types upregulated TLR1 and TLR6. Only type 2 infection upregulated TLR3, but downregulated TLR4 and TLR8. By contrast, both types upregulated TLR4 and downregulated TLR6 protein expression. Interleukin (IL)-1{beta}, IL-6 and tumor necrotic factor (TNF)- were upregulated by type 2, but IL-8 was upregulated by type 1. Both PRRSV type 1 and 2 stimulated IL-6 but suppressed TNF- secretion. In addition, IL-1{beta} secretion was suppressed by type 2. These findings reveal one of the important mechanisms underlying the strategy of PRRSV on innate immune evasion in endometrium which is associated with the viral persistence. Author SummaryWidely prevalence of porcine reproductive and respiratory syndrome virus (PRRSV) remains the leading cause of huge economic losses to the global swine industry. Due to an infection of macrophages, PRRSV can persist in animals for extended periods of time associated with long-lasting reproductive disorders. Modification of cellular and immunological responses to PRRSV infection which may be related with the pathogenesis of reproductive disorders remains unclear. Herein, direct PRRSV infection of primary porcine glandular endometrial epithelial cell culture (PGE) demonstrated that PRRSV type 1 and 2 upregulated the protein expression of PRRSV mediators correlated with cell persistence of PRRSV. However, TLR and cytokines gene expression, and cytokine secretion were differentially modulated in response to PRRSV type 1 vs. type 2. Our study provides new insights into the cellular mechanism associating with PRRSV persistence in the endometrial cells and the underlying interaction of virus with the host.