Orthohantavirus infection is a rodent-to-human zoonotic disease with a worldwide distribution, resulting in more than 200,000 cases per year. Human infection leads to two diseases, haemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome, with mortality rates ranging from 1% to 38%. Apart from the data on cases presenting obvious clinical symptoms, the true prevalence is poorly understood, especially in the occupational groups considered to be at risk of exposure. As there is currently no approved therapy or vaccine, surveillance is essential to locate the presumed site of infection following orthohantavirus outbreaks in order to control the spread of infection. To this end, the use of rapid diagnostic tools is essential to rapidly provide data on viral circulation. This review focuses mainly on the available diagnostic methods, both serological and biomolecular, and the surveillance systems used for orthohantaviruses. The information gathered could provide a valid basis for the implementation of further surveillance systems in a country lacking up-to-date data.

INTRODUCTION: The intronic MAPT mutation IVS10+16 is linked to familial frontotemporal dementia, causing hyperphosphorylation and accumulation of tau protein, resulting in synaptic and neuronal loss and neuroinflammation in patients. This mutation disrupts MAPT gene splicing, increasing exon 10 inclusion and leading to an imbalance of 3R and 4R Tau isoforms.METHODS: We generated patterned cortical organoids from isogenic control and mutant human induced pluripotent stem cell (iPSC) lines. Nanostring gene expression analysis, immunofluorescence, and calcium imaging recordings were used to study the impact of the MAPT IVS10+16 mutation on neuronal development and function.RESULTS: Tau mutant cortical organoids showed altered mitochondrial function and gene expression related to neuronal development, with synaptic markers and neuronal activity reduction. Bezafibrate treatment restored mitochondrial content and rescued synaptic functionality and tau physiology.DISCUSSION: These findings suggest that targeting mitochondrial function with bezafibrate could potentially reverse tau‐induced neurodevelopmental deficits, highlighting its therapeutic potential for tauopathies like frontotemporal dementia.Highlights: The IVS 10+16 MAPT mutation significantly disrupts cortical differentiation and synaptic maturation, evidenced by downregulated genes associated with synapses and neuronal development. Tau‐mutant cortical organoids exhibit mitochondrial dysfunction, with fewer and smaller mitochondria alongside tau hyperphosphorylation and aggregation, which further contribute to neuronal damage and disease progression. Treatment with bezafibrate effectively normalizes mitochondrial parameters, enhances neuronal integrity and synaptic maturation, and restores network functionality, showcasing its promise as a therapeutic strategy for tauopathies. The 3D in vitro disease model used in this study proves valuable for studying tauopathies and testing new drugs, effectively mimicking key aspects of tau‐related neurodegeneration.

Statins are inhibitors of the mevalonate pathway that besides being cholesterol lowering agents, display anti‐cancer properties. This is because cholesterol is an essential component of cell membranes but also because the mevalonate pathway controls protein farnesylation and geranylation, processes essential for the activity of GTPase family proteins. In this study, we found that Lovastatin exerted a dose‐ and time‐dependent cytotoxic effect against PEL cells, an aggressive B cell lymphoma strictly associated with the gammaherpesvirus KSHV and characterized by a poor response to conventional chemotherapies. At molecular level, Lovastatin by dephosphorylating STAT3, induced ERK1/2 activation that inhibited autophagy and phosphorylated p53ser15 that in turn maintained ERK1/2 activated and up‐regulated p21. However, p21 played a pro‐survival role in this setting, as its inhibition by UC2288 further reduced cell survival in PEL cells undergoing Lovastatin treatment. In conclusion, this study suggests that Lovastatin may represent a valid therapeutic alternative against PEL cells, especially if used in combination with p21 inhibitors.

Rift Valley Fever virus (RVFV) is a mosquito-borne virus with high pathogenic potential in ruminants and humans. Due to its high potential for spreading, it is considered a priority pathogen, and it is included in the Bluepoint list of the World Health Organization (WHO). Given the high pathogenic potential of the virus, it is crucial to develop a rapid heat-mediated inactivation protocol to create a safer working environment, particularly in medical facilities that lack a biosafety level 3 laboratory required for direct handling of RVFV. Our results reveal the broad tissue tropism of RVFV, showing the virus’s capacity for replication in various cell lines. In terms of the thermal stability of RVFV, our findings showed that a 70 °C heat treatment did not fully inactivate the virus within 15 min. However, when exposed to 80 °C and 95 °C, the virus was completely inactivated after 15 min and 5 min, respectively. Additionally, our results indicated that heat-treatment only slightly decreased the integrity of the RVFV genome whether there is a high or low number of viral RNA copies. Overall, the study established a straightforward protocol for heat inactivation that may be beneficial in handling clinical and research samples of RVFV.

The Orthobunyavirus Oropouche (OROV) has become an urgent public health threat in Central and South America, as well as in other countries worldwide. Since its initial identification, there have been over 30 outbreaks, with the largest reported in late 2024 in Brazil. This outbreak prompted an epidemiological alert due to a significant increase in OF cases in non-Amazonian states in the Americas region, as well as in European countries, where 44 imported cases were identified. Humans become infected predominantly through the bite of the Culicoides paraensis midge, and the symptoms could be misinterpreted due to their similarity to those of other arboviral infections. Due to the lack of a point-of-care test, RT-qPCR is currently the key diagnostic test during the acute phase of the disease. This review focuses primarily on the available molecular and serological diagnostic methods. The latter could indeed be used as a confirmation test to monitor the patient’s immunological status and better distinguish between cross-reacting arboviruses. In addition, this review explains also the existing sequencing methods required to enforce the surveillance system for OROV reassortant species that could cause a new worldwide outbreak. The information gathered could provide a valuable basis for implementing additional surveillance systems in those countries lacking up-to-date data.

Rift Valley Fever Virus (RVFV) is an arbovirus that predominantly affects sheep, goats, and cattle, causing epizootics in livestock and epidemics in humans. Infection in pregnant livestock leads to high abortion rates and neonatal mortality. In humans, RVFV usually causes a self-limiting febrile illness, but severe forms can develop, such as hepatitis, hemorrhage, encephalitis, and death. In addition, the association between RVFV infection during pregnancy and miscarriages or stillbirths has been documented. RVFV is transmitted by a range of mosquito species, and, due to the diffusion of these insects, the virus has spread in several world regions, making possible the risk of a public health emergency. Nevertheless, research remains limited and cellular pathology is still poorly characterized. This work aimed to fill some knowledge gaps on the comprehension of RVFV pathogenesis. For this purpose, transmission electron microscopy (TEM) was used to analyze cellular modifications associated with RVFV morphogenesis in four human cell lines (HuH-7, LAN-5, A549, and HTR-8/SVneo) derived from liver, brain, lung, and placenta. Our results showed that all four cell lines are permissive to RVFV infection and highlighted differences in the cytopathogenesis associated with the cell type. These findings could have important implications in understanding disease mechanisms and developing antiviral strategies.