Strain-dependent differences in the capacity of peste des petits ruminants virus to infect antigen-presenting cells

ABSTRACT The ability of morbilliviruses to infect antigen-presenting cells (APCs) plays a major role in infection outcome, because these cells transport peste des petits ruminants virus (PPRV) from the respiratory tract to the lymph nodes before spreading to lymphoid and epithelial tissues. This study used two cell models, — monocyte-derived macrophages (MoMs) and monocyte-derived dendritic cells (MoDCs), — from three host species (goat, sheep and cattle) to evaluate the differential ability of APCs to be infected by two strains of PPRV with contrasting virulence in goats. Infection was analysed using flow cytometry, infectious titers (TCID₅₀/mL), RT-qPCR and immunofluorescence. Goat and sheep MoDCs proved highly permissive to both strains, with viral titers at 48 hpi in the range of 10⁴–10⁵ TCID₅₀/mL and a high percentage of infected cells. Cattle MoDCs were weakly infected and had no detectable viral titer, as expected for this dead-end host. In comparison, MoMs showed reduced permissiveness to PPRV in goats but not in sheep. Post-infection supernatants in goat MoMs infected with the low-virulent strain showed low or undetectable TCID₅₀/mL, despite persistence of detectable viral genome up to 96 hpi. Immunofluorescence revealed double-stranded RNA but no nucleoprotein of the low-virulent strain in goat MoMs, suggesting a partial engagement of the viral cycle, resulting in a restricted or semi-permissive infection. Overall, these results suggest that this combined in vitro model of MoDC and MoM infections would be useful in anticipating host susceptibility and PPRV strain virulence, providing complementary tools for PPR control efforts. IMPORTANCE Peste des petits ruminants (PPR) disease affects goats, sheep and multiple other hosts across the globe, with major impacts on economies, food security and biodiversity. The sensitivity of host species to PPRV infection varies considerably, with clinical manifestations and disease progression being shaped by the viral strain, host species and breed infected. In vitro models focusing on immune cells, which are the primary target of PPRV could provide a relevant tool for studying the mechanisms of viral adaptation to the host and cellular antiviral responses, while contributing to surveillance and control strategies. The results obtained here suggest that a dual-cell model focusing on macrophages and dendritic cells could be useful for pre-screening studies aimed at assessing the susceptibility of a given host species to a PPRV strain and estimating its relative virulence. Testing this in vitro approach in additional host species and a wider range of strains is required to confirm its relevance. Competing Interest Statement The authors have declared no competing interest. Footnotes The order of authors reflects the relative contributions of the individuals listed up to S. Guendouz. The last three authors, P. Holzmuller, P. Totté, and A. Bataille, contributed to the study in supervisory roles. This revised version of the manuscript has been shorten to clarify the introduction and discussion of the study. Statistical analyses have been revised. Figures have been re-organised for clarity. Additional information regarding the characterisation of the cell populations has been added. The interpretation of the results regarding dsRNA staining has been revised.