Biology subjects

Holzmuller, P.

Publications and source records attributed to Holzmuller, P..

3 recordsLinked to original sources

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↗

bioRxiv2025

First detection of Crimean Congo Hemorrhagic Fever antibodies in cattle and wild fauna of southern continental France: investigation of explicative factors

Crimean-Congo Haemorrhagic Fever (CCHF) is a tick-borne zoonosis with significant public health implications due to its expanding geographic distribution and potential for severe outcomes in humans. This study represents the first serological survey conducted in mainland France to detect antibodies against the Crimean-Congo Haemorrhagic Fever Virus (CCHFV) in domestic and wild fauna, providing critical insights into the viruss circulation. We analyzed 8,609 cattle sera and 2,182 wildlife sera collected across the French Mediterranean region from 2008 to 2022, using enzyme-linked immunosorbent assays (ELISA) and pseudo-plaque reduction neutralization tests (PPRNT) for antibody detection and confirmation. Seropositivity was detected in both cattle (2.04%) and wildlife (2.25%), with higher rates observed in specific regions such as Pyrenees-Orientales and Hautes-Pyrenees. These findings reveal spatial clusters of CCHFV circulation and suggest the existence of enzootic transmission cycles involving local tick vectors and animal hosts. Our multivariate analysis identified key factors influencing seropositivity, including animal age, habitat characteristics, and potential wildlife interactions. The presence of natural open habitats and coniferous forests was significantly associated with higher seropositivity in cattle, while sex and geographical variability played a role in wildlife seroprevalence. These findings highlight the importance of environmental and anthropogenic factors in shaping the dynamics of CCHFV transmission. This study demonstrates that CCHFV is actively circulating in parts of mainland France, emphasizing the need for enhanced surveillance and integrated approaches to monitor zoonotic pathogens. It also raises questions about the role of additional tick vectors, such as Hyalomma lusitanicum, in the transmission cycle. These results contribute to a better understanding of CCHF epidemiology and offer valuable guidance for public health strategies to mitigate the risks associated with this emerging disease. Author SummaryCrimean-Congo Haemorrhagic Fever (CCHF) is a severe disease spread by ticks that affects humans and animals. Although the disease is largely distributed in parts of Europe, Africa, and Asia, its presence in France has been uncertain. My study investigated whether the virus causing this disease is circulating in southern mainland France by testing blood samples from domestic animals, like cattle, and wild animals, such as deer and wild boars, for signs of previous infection. I found evidence of the virus in several regions, particularly in the Pyrenees-Orientales, Hautes-Pyrenees and Alpes-maritimes, suggesting that the virus is indeed circulating among animals and ticks in some parts of mainland France. By studying where infected animals were found and considering factors such as age, habitat, and environmental conditions, I identified that older animals seem to have been more often exposed to the virus, as well as animals frequenting open environments favorable to ticks. These findings are important because they show that the disease could potentially spread to new areas and affect human populations. My work highlights the need for ongoing monitoring of ticks and animals for CCHFV epidemiological surveillance and the protection of public health.

ecology↗

bioRxiv2024

Tick-borne pathogens identified in Hyalomma marginatum (Acari: Ixodidae) collected from various vertebrate hosts in the South of France

Hyalomma marginatum is a common ectoparasitic tick of ungulates, lagomorphs, insectivores, ground-foraging birds, observed in Corsica for decades, but whose permanent establishment in mainland France is very recent. This species is known to be one of the main vectors of the Crimean-Congo Hemorrhagic Fever virus, but also of various parasitic, bacterial or viral pathogens. In this study, we investigated the molecular infection rates of numerous tick-borne pathogens in H. marginatum ticks mainly sampled on horses, and occasionally on other animal species, from the French Mediterranean rim and Corsica between 2016 and 2020. In total, 1, 195 DNA and RNA purified from individual ticks or pools of ticks were screened for 26 microbial genera or species (viruses, bacteria and parasites), using a high-throughput microfluidic real-time PCR system (BioMark dynamic array system, Standard Biotools). For individual ticks and pooled ones, respectively, the most prevalent tick-borne microorganisms were Francisella-like endosymbionts at 97.0% and 96.8%, followed by Rickettsia aeschlimannii (76.4% and 96.4%), Theileria spp. and Theileria equi (3,5% and 0%; 1,9% and 5,8%), Anaplasma phagocytophilum (3.7% and 6.7%), and West Nile virus (0.1% and 0.4%). Babesia occultans (0.9%), Ehrlichia minasensis (0.3%), and Coxiella-like endosymbionts (0.1%) were only detected in individual ticks. Our study provides an overview of the diversity of microorganisms and tick-borne pathogens detected in the invasive tick H. marginatum in Corsica and the continental departments of the Mediterranean rim. Our study opens up new research perspectives on the epidemiology of tick-borne pathogens carried by H. marginatum and on the associated public and veterinary health risks.

microbiology↗