Integrated Downstream Analysis and Epidemiological Modelling of Hantavirus Infection: From Host Transcriptomics to Transmission Dynamics

Hantaviruses are emerging zoonotic pathogens responsible for two severe clinical syndromes: (i) haemorrhagic fever with renal syndrome (HFRS) and (ii) hantavirus cardiopulmonary syndrome (HCPS), collectively causing more than 200,000 human cases annually worldwide. Despite their public-health importance, the molecular mechanisms governing the host response and the population-level dynamics of rodent- to-human spillover remain incompletely characterised. The timeliness of this frame- work is underscored by the April–May 2026 outbreak of Andes orthohantavirus aboard 9 the MV Hondius cruise ship – the first such cluster in a maritime setting, with three deaths reported across multiple countries (WHO Disease Outbreak News: https://www.who.int/emergencies/disease-outbreak-news/item/2026-DON599). This event revealed critical gaps in existing models that treat humans solely as dead-end spillover hosts. Here, we present an integrated computational study that combines three complementary analyses. Preliminarly, we performed the first phylogenetic analysis of such virus, idenifying as Orthoantavirus andensense the responsible for the vessel outbreak. Second, we performed a downstream transcriptomic analysis of Hantaan virus (HTNV)-infected human umbilical vein endothelial cells (HUVECs) using publicly available RNA-seq data (GEO accession GSE133751, n = 3 per group), identifying 184 upregulated and 19 downregulated evidencing the role of dominated by interferon-stimulated genes (ISGs), including CXCL10, CXCL11, MX2, DDX58, IRF7, STAT1, OASL, and CMPK2. We constructed a protein–protein interaction (PPI) network from STRING (176 nodes, 3,210 edges) and applied a composite network centrality score to rank regulatory hubs, identifying ISG15, IRF1, CXCL10, STAT1, and DDX58 as the most central nodes. Pathway enrichment analysis con- firms strong activation of interferon signalling (Reactome, p = 1.3×10⁻⁶³), antiviral defence (Gene Ontology, p = 3.8 × 10⁻⁵⁸), and NF-κB pathways, with concurrent suppression of ribosomal translation. We finally developed a coupled SEIRD epi-demiological model that explicitly represents rodent-to-rodent and rodent-to-human transmission with logistic rodent population growth. Preliminary simulation analysis demonstrates that reducing human exposure to rodent excreta is substantially more effective than rodent population control alone for reducing human disease burden, and that rodent control in isolation can paradoxically increase human cases through a dilution-like effect. The integrated framework provides molecular and epidemiological insights relevant to hantavirus surveillance, therapeutic target identification, and 35 public-health intervention design.