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Background Ebola (EBOV) and Sudan (SUDV) orthoebolaviruses are responsible for lethal hemorrhagic fever outbreaks in humans in Central and West Africa, and in apes that can be at the source of human outbreaks for EBOV. Methods To assess the risk of exposure to orthoebolaviruses through contact with nonhuman primates (NHP), we tested the presence of antibodies against different viral proteins with a microsphere-based multiplex immunoassay in a case-control study on bites from NHPs in forest areas from Cameroon (n = 795) and in cross-sectional surveys from other rural populations (n = 622) of the same country. Results Seroreactivities against at least 2 viral proteins were detected in 13% and 12% of the samples for EBOV and SUDV, respectively. Probability of seroreactivity was not associated with history of NHP bites, but was 3 times higher in Pygmies compared to Bantus. Although no neutralizing antibodies to EBOV and SUDV were detected in a selected series of highly reactive samples, avidity results indicate strong affinity to SUDV antigens. Conclusions The detection of high level of seroreactivities against orthoebolaviruses in rural Cameroon, where no outbreaks have been reported, raises the possibilities of silent circulation of orthoebolaviruses, or of other not yet documented filoviruses, in these forested regions. Article's main point Our study found high seroreactivities to Ebola and Sudan orthoebolavirus antigens in rural Cameroonian populations, especially among Pygmies, despite no reported outbreaks. This suggests potential silent circulation of orthoebolaviruses or unknown filoviruses, highlighting the need for further surveillance and research. [ABSTRACT FROM AUTHOR]

Lassa fever is endemic to western Africa. Nigeria, Guinea, Sierra Leone, and Liberia regularly have outbreaks of Lassa fever, mostly during the first few months of the year, corresponding to [...]

The pathogenesis of Lassa fever has not yet been fully deciphered, particularly as concerns the mechanisms determining whether acute infection is controlled or leads to catastrophic illness and death. Using a cynomolgus monkey model of Lassa virus (LASV) infection reproducing the different outcomes of the disease, we performed histological and transcriptomic studies to investigate the dynamics of LASV infection and the immune mechanisms associated with survival or death. Lymphoid organs are an early major reservoir for replicating virus during Lassa fever, with LASV entering through the cortical sinus of draining lymph nodes regardless of disease outcome. However, subsequent viral tropism varies considerably with disease severity, with viral dissemination limited almost entirely to lymphoid organs and immune cells during nonfatal Lassa fever. By contrast, the systemic dissemination of LASV to all organs and diverse cell types, leading to infiltrations with macrophages and neutrophils and an excessive inflammatory response, is associated with a fatal outcome. These results provide new insight into early viral dynamics and the host response to LASV infection according to disease outcome. Author summary: Lassa fever, induced by Lassa virus, is a viral hemorrhagic fever of great concern as it is endemic to a large part of Africa, with tens of thousands of cases per year, and there is no effective treatment or licensed vaccine. Lassa virus can be handled only in biosafety level 4 facilities and access to patients is limited. As a result, little is known about the pathogenesis of this severe disease. Non-human primates, and macaques in particular, are the most relevant animal models for studies of this disease. We previously developed a cynomolgus monkey model reproducing the different outcomes of Lassa fever observed in humans: limited clinical signs and recovery versus catastrophic illness and death. Here, we use this model to investigate further the dynamics of Lassa virus dissemination, cell tropism in different organs, and host response to infection. Our findings demonstrate that cell tropism and viral dissemination differ considerably between outcomes, underlying the different host responses to Lassa virus infection and differences in severity. [ABSTRACT FROM AUTHOR]

Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related, rodent-born mammarenaviruses. LASV is the causative agent of Lassa fever, a deadly hemorrhagic fever endemic in West Africa, whereas MOPV is non-pathogenic in humans. The Z matrix protein of arenaviruses is essential to virus assembly and budding by recruiting host factors, a mechanism that remains partially defined. To better characterize the interactions involved, a yeast two-hybrid screen was conducted using the Z proteins from LASV and MOPV as a bait. The cellular proteins ITCH and WWP1, two members of the Nedd4 family of HECT E3 ubiquitin ligases, were found to bind the Z proteins of LASV, MOPV and other arenaviruses. The PPxY late-domain motif of the Z proteins is required for the interaction with ITCH, although the E3 ubiquitin-ligase activity of ITCH is not involved in Z ubiquitination. The silencing of ITCH was shown to affect the replication of the old-world mammarenaviruses LASV, MOPV, Lymphocytic choriomeningitis virus (LCMV) and to a lesser extent Lujo virus (LUJV). More precisely, ITCH was involved in the egress of virus-like particles and the release of infectious progeny viruses. Thus, ITCH constitutes a novel interactor of LASV and MOPV Z proteins that is involved in virus assembly and release. [ABSTRACT FROM AUTHOR]

Few data are available regarding the role of human skin dendritic cells (DCs) in driving T-cell responses. In this study we analyzed the relative capacity of Langerhans cells (LCs) and dermal CD14−CD1c+ DCs (DDCs) to trigger naive CD4+ T-cell proliferation and differentiation. DC subsets were purified after a 2-day migration from epidermis and dermis of the same skin sample. Migratory LCs showed far more activated phenotype than CD1c+DDCs and distinct expression of new molecules of the B7 family; when compared with LCs, CD1c+DDCs showed higher PD-L1 and lower inducible co-stimulator ligand (ICOS-L) expression. As expected, CD1c+DDCs showed lower allostimulatory property than LCs, a process that was partly reversed by anti-PD-L1 mAb. LCs were significantly more efficient than CD1c+DDCs at inducing allogeneic naive CD4+ T cells to secrete both T helper cell 1 (Th1; IFN-γ and tumor necrosis factor-α ) and Th2 (IL-4 and IL-5) cytokines. Moreover, anti-PD-L1 mAb increased the production of IFN-γ by both LC- and CD1c+DDC-stimulated T cells. Globally, these results argue for a preponderant role of human LCs in inducing naive CD4+ T-cell priming. Low expression of co-stimulatory molecules together with high expression of PD-L1 might limit the efficiency of CD1c+DDCs at inducing naive CD4+ T-cell proliferation and secretion of cytokines. [ABSTRACT FROM AUTHOR]

Crimean-Congo haemorrhagic fever (CCHF), a potentially severe zoonotic viral disease causing fever and haemorrhagic manifestations in humans. As the Crimean-Congo haemorrhagic fever virus (CCHFV) has been detected in ticks in Spain and antibodies against the virus in ruminant sera in Corsica, it was necessary to know more about the situation in France. In 2022-2023, CCHFV was detected in 155 ticks collected from horses and cattle in southern France.

Few data are available regarding the role of human skin dendritic cells (DCs) in driving T-cell responses. In this study we analyzed the relative capacity of Langerhans cells (LCs) and dermal CD14(-)CD1c(+) DCs (DDCs) to trigger naive CD4(+) T-cell proliferation and differentiation. DC subsets were purified after a 2-day migration from epidermis and dermis of the same skin sample. Migratory LCs showed far more activated phenotype than CD1c(+)DDCs and distinct expression of new molecules of the B7 family; when compared with LCs, CD1c(+)DDCs showed higher PD-L1 and lower inducible co-stimulator ligand (ICOS-L) expression. As expected, CD1c(+)DDCs showed lower allostimulatory property than LCs, a process that was partly reversed by anti-PD-L1 mAb. LCs were significantly more efficient than CD1c(+)DDCs at inducing allogeneic naive CD4(+) T cells to secrete both T helper cell 1 (Th1; IFN-gamma and tumor necrosis factor-alpha ) and Th2 (IL-4 and IL-5) cytokines. Moreover, anti-PD-L1 mAb increased the production of IFN-gamma by both LC- and CD1c(+)DDC-stimulated T cells. Globally, these results argue for a preponderant role of human LCs in inducing naive CD4(+) T-cell priming. Low expression of co-stimulatory molecules together with high expression of PD-L1 might limit the efficiency of CD1c(+)DDCs at inducing naive CD4(+) T-cell proliferation and secretion of cytokines.