Strain-dependent differences in the capacity of Peste des Petits Ruminants virus to infect antigen presenting cells

Abstract

ABSTRACT The ability of morbilliviruses to infect antigen-presenting cells (APCs) plays a major role in the outcome of infection, as these cells transport the virus 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, cattle), to evaluate the differential ability of APCs to be infected by two strains of peste des petits ruminants virus (PPRV) with contrasting virulence in goats. Infection was analyzed by flow cytometry, infectious titers (TCID₅₀/mL), RT-qPCR and immunofluorescence. Goat and sheep MoDCs proved highly permissive to both virus strains, with viral titers at 48 hpi in the range of 10⁴–10⁵ TCID₅₀/mL and a high percentage of infected cells, unlike bovine MoDCs, which 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 analyses revealed the presence of double-stranded RNA but absence of nucleoprotein of the low virulent PPRV strain in goat MoMs suggests a blockage at the level of viral protein translation. 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 the economy, food security and biodiversity. The sensitivity of the host species to PPR virus infection varies considerably, with clinical manifestations and disease progression being shaped by the viral strain, host species, and infected breed. 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.

Affiliated Institutions

• Animal, Santé, Territoires, Risques et Ecosystèmes FR
• Centre de Coopération Internationale en Recherche Agronomique pour le Développement FR
• Institut de Génétique Moléculaire de Montpellier FR
• Université de Poitiers FR
• Centre de Résonance Magnétique des Systèmes Biologiques FR

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