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LITERATURE UPDATE


responses, trans-signalling can cause severe pathogenic responses. Here, the authors investigated a potential role for IL-6 trans-signalling in hantavirus pathogenesis. Effects of IL-6 trans-signalling during


in vitro hantavirus infection were assessed using primary human endothelial cells treated with recombinant soluble IL-6 receptor (sIL-6R). Plasma from Puumala orthohantavirus-infected HFRS patients (n=28) were analysed for IL-6 trans- signalling potential and its associations to severity. In vitro, sIL-6R treatment of infected


The western deer mouse, a rodent native to North America, and the natural reservoir of Sin Nombre hantavirus.


These antibodies are freely available to all hantavirus researchers to add to the small, but growing, collection of reliable and available reagents to be used to study hantavirus biology, identify novel antiviral compounds, and measure viral prevalence in the laboratory and the field. Pathogenic hantaviruses cause


severe haemorrhagic disease and pose a significant public health threat worldwide. Insufficient research into the biology of these viruses has slowed the development of effective direct-acting antivirals and vaccines. Here, the authors describe the generation and validation of novel, specific monoclonal antibodies for the detection of Seoul virus proteins in vitro. These reagents can be used to fill in critical gaps in knowledge regarding hantavirus entry, protein expression, and particle generation.


Interactions Between Hantavirus Nucleoprotein and Glycoproteins: A Quantitative Fluorescence Microscopy Study Aji AK, Mandal T, Chiantia S. Viruses. 2025 Jul 2; 17 (7): 940. doi: 10.3390/v17070940.


Orthohantaviruses are tri-segmented negative-sense RNA viruses that can cause severe pathologies in humans. Currently, limited information exists on the molecular interactions driving orthohantavirus assembly in infected cells. Specifically, it is not clear how its glycoproteins (ie Gn and Gc) interact with other viral or host molecules. In this study, the authors use one-


and two-colour Number and Brightness fluorescence microscopy approaches to quantitatively characterise the interactions between orthohantavirus


glycoproteins and the nucleoprotein in transfected cells. The results indicate that orthohantavirus nucleoprotein homo-interactions are strongly affected by the host environment. Furthermore, the authors report evidence of Gc- nucleoprotein interactions, based on i) the high fluorescence cross-correlation between these two proteins and ii) the increased Gc-Gc interactions observed in the presence of nucleoprotein. Finally, experiments on a Gc deletion mutant suggest that the observed protein- protein interactions are mediated by the cytoplasmic tail of Gc. In conclusion, this study provides new insights into the role of the interactions between orthohantavirus glycoproteins and nucleoprotein in the context of viral assembly.


IL-6 trans-signaling mediates cytokine secretion and barrier dysfunction in hantavirus-infected cells and correlates to severity in HFRS Maleki KT, Niemetz L, Christ W et al., PLoS Pathog. 2025 Apr 9; 21 (4): e1013042. doi: 10.1371/journal.ppat.1013042. eCollection 2025 Apr.


Hantavirus causes haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Strong inflammatory responses and vascular leakage are important hallmarks of these often fatal diseases. The mechanism behind pathogenesis is unknown and no specific treatment is available. Interleukin-6 (IL-6) was recently highlighted as a biomarker for HPS/ HFRS severity. IL-6 signalling is complex and context dependent: while classical signalling generally provides protective


cells enhanced IL-6 and CCL2 secretion, upregulated ICAM-1, and affected VE- cadherin leading to a disrupted cell barrier integrity. HFRS patients showed altered plasma levels of sIL-6R and soluble gp130 (sgp130) resulting in an increased sIL-6R/sgp130 ratio suggesting enhanced IL-6 trans-signalling potential. Plasma sgp130 levels negatively correlated with number of interventions and positively with albumin levels. Patients receiving oxygen treatment displayed a higher sIL- 6R/sgp130 ratio compared to patients that did not. IL-6 trans-signalling is linked to


hantavirus pathogenesis. Targeting IL-6 trans-signalling might provide a therapeutic strategy for treatment of severe HFRS and perhaps also HPS.


Orthohantaviruses: An Overview of the Current Status of Diagnostics and Surveillance Romeo MA, Tofani S, Lapa D et al. Viruses. 2025 Apr 26; 17 (5): 622. doi: 10.3390/v17050622.


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


June 2026 WWW.PATHOLOGYINPRACTICE.COM 53


USFWS Mountain-Prairie Public domain Wikimedia Commons


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