Lasserre, V. | Search bioRxiv

bioRxiv2025

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

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 (TCID/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 10-10 TCID/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 TCID/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. IMPORTANCEPeste 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.

microbiology↗

bioRxiv2024

Peste des Petits Ruminants virus virulence is associated with an early inflammatory profile in the tonsils and cell cycle arrest in lymphoid tissue

Using a systems immunology approach, this study comprehensively explored the immunopathogenesis of Peste des Petits Ruminants (PPR) focussing on strain-dependent differences in virulence. Saanen goats were infected either with the highly virulent Morroco 2008 (MA08) or the low virulent Ivory Coast 1989 (IC89) strain of PPR virus (PPRV). As expected, MA08-infected goats exhibited higher clinical scores, pronounced lymphocyte depletion, and lesions affecting mucosal and lymphoid tissues. CD4 T cells were found to be most affected in terms of depletion and infection in the peripheral blood. Transcriptional analyses of the blood and lymphoid tissue demonstrated activation of interferon type I (IFN-I) responses at three days post infection (dpi) only with MA08, but comparable IFN-I expression levels with MA08 and IC89 at 6 dpi. In contrast, only the MA08 strain induced strong inflammatory and myeloid cell-related transcriptional responses which as observed in tonsils but not in the mesenteric lymph node. This inflammatory response in the tonsil was associated with an extensive damage and infection of the tonsillar epithelium in the crypts, pointing on a barrier defect as a possible cause of inflammation. The other prominent effect induced by MA08, but not IC89, was a strong and early downregulation of cell cycle gene networks in lymphoid tissues. This effect was found in the blood compartment and all analysed lymphoid tissues and can be interpreted as suppressed lymphocyte proliferation that may cause immunosuppression during the first week following MA08 infection. A proteome analysis confirmed elevated synthesis of IFN-I response proteins during infection with both strains, but only the MA08 strain additionally upregulated ribosomal and inflammation-related proteins. In conclusion, the present comprehensive investigation delineates strain-dependent differences in early immunopathological processes associated with severe inflammation disease and a blunted lymphocyte proliferation. Understanding such strain-specific differences is relevant for effective PPRV surveillance strategies. Author summaryField observations show that the severity of infection with Peste des Petits Ruminants virus (PPRV) is highly dependent on the viral strains and the host infected, but the mechanisms behind these variations are not well understood. Here we compare immune response in Saanen goats infected with high (MA08) and low (IC89) virulent PPRV strains. Analyses revealed a differential immune response: early activation of type I interferon (IFN-I) responses only with MA08, but comparable IFN-I expression levels with MA08 and IC89 at later stages. Additionally, only the MA08 strain triggered inflammatory and myeloid cell- related responses in the tonsils, as well as a disseminated early and marked suppression of lymphocyte proliferation evidenced by cell cycle arrest. CD4 T cells were found to be most affected in terms of depletion in the peripheral blood. Massive infection of the tonsils, particularly for the highly virulent strains, seems to induce epithelial lesions that promotes the inflammatory responses. These findings underscore the importance of understanding strain- specific differences for appropriate surveillance and control of PPR.

immunology↗