Biology subjects

Piumi, F.

Publications and source records attributed to Piumi, F..

3 recordsLinked to original sources

bioRxiv2026

Characterization of emerging Oropouche virus tropism and pathogenicity.

BackgroundOropouche virus is an emerging arbovirus increasingly associated with neurological complications, but its human cellular tropism and potential routes to the central nervous system remain poorly defined. This study aimed to characterize infection across clinically relevant human cell types and to investigate interactions with a human blood-brain barrier model and human neuronal/glial cells. MethodsA panel of human cell lines and primary human cells relevant to systemic and neurological disease was infected with Oropouche virus. Viral replication and production of infectious particles were quantified using molecular assays and infectivity titrations, and viral protein expression was assessed by immunoblotting and immunofluorescence. Barrier crossing was evaluated using a Transwell brain endothelial model with permeability monitoring, and infection dynamics in neuronal/glial cultures derived from human neural progenitors were quantified by imaging-based analyses. Group comparisons used non-parametric tests with Dunn-Bonferroni correction and Mann-Whitney tests; neuronal/glial cell counts were analysed using linear models with Fisher tests for interaction terms and multiplicity-adjusted post hoc comparisons. ResultsOropouche virus productively infected hepatocyte-like and intestinal epithelial cells, with high viral RNA output and release of infectious progeny. Primary synoviocytes, chondrocytes and skeletal muscle cells were permissive but produced lower infectious titers. Brain endothelial cells were inoculated and virus was progressively detected in the basolateral compartment, while endothelial permeability remained unchanged, indicating barrier crossing without disruption. In neuronal/glial cultures, both neurons and astrocytes were susceptible; infection was associated with marked cytopathic changes and a preferential, accelerated decline in neuron abundance over time. ConclusionsThese findings demonstrate broad human cell tropism and support blood-brain barrier crossing without major loss of barrier integrity, alongside pronounced neuronal vulnerability. The described models provide a platform to dissect mechanisms of neuroinvasion and to evaluate targeted antiviral strategies.

microbiology↗

bioRxiv2025

Oropouche virus infects human neural progenitor cells and alters the growth of brain organoids

Oropouche virus (OROV), is the etiologic agent of Oropouche fever (OROF), an emerging zoonotic disease that has been prevalent in South and Central America since the 1960s. Starting late 2023, the current outbreak has raised concern about vertical transmission and potential adverse pregnancy outcomes. While serological evidences and recent studies support the vertical transmission of OROV, how infection affects the fetal brain remains unclear. Here we show that a strain of OROV, FG_2020, phylogenetically-related to the epidemic strain, efficiently and productively infects human neural progenitor cells and iPSC-derived brain organoids. The main phenotypic effect is proliferation arrest associated with apoptosis leading to the loss of neural rosette organization, a key signature of developing brain architecture. These data indicates that fetal brain is susceptible to OROV infection and that vertical transmission during the first months of pregnancy could lead to pathological effects on brain development.

microbiology↗

bioRxiv2022

Integrated protein-protein interaction and RNA interference screens reveal novel restriction and dependency factors for a tick-borne flavivirus in its human host

In Europe, tick-borne encephalitis virus (TBEV) is responsible for severe neurological disease in humans. Like other viruses, TBEV is an obligate intracellular life form whose survival requires subversion of metabolic processes and evasion of anti-viral pathways. This feat is achieved in no small part by binary interactions between dedicated viral proteins and host proteins. Such protein-protein interactions (PPI) constitute molecular determinants of critical pathobiologic traits of viruses, including host-range, zoonotic potential and virulence, and represent realistic targets for anti-viral therapies. To shed light on the pathobiology of TBEV in human, we have resolved the network of PPI established with its human host by interaction proteomics. A high-throughput screen for virus-host PPI was performed involving the complete set of open reading frames of TBEV and the cDNA libraries of Homo sapiens, by means of yeast two-hybrid methodology. We have discovered a large set of virus-host protein-protein interactions concerning 42 different human proteins directly interacting with nine viral proteins. Many of these human interactors have never been linked in the literature to viral infection. The functional significance of the host interactors in viral infection as viral dependency or restriction factors was then characterized in vitro by RNA interference, and their function inferred by bioinformatic analysis. Approximately 40% of the identified human proteins have a significative impact on TBEV viral replication. These are engaged in many biological processes, whose involvement in viral infection is expected for many, but enigmatic for some. Further work will be necessary to gain molecular understanding of how these biological processes support or restrict TBEV replication, and whether they constitute viral vulnerabilities that can be exploited therapeutically.

microbiology↗