AbstractHantaviruses are emerging zoonotic pathogens belonging to the family Hantaviridae that pose significant global public health threats. Traditionally associated with rodent reservoirs, recent discoveries have expanded their ecological range to include shrews, moles, and bats, indicating a more complex evolutionary history than previously recognized. Human infection occurs primarily through inhalation of aerosolized excreta from infected reservoir hosts, leading to severe diseases such as hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). Evolutionary mechanisms including host switching, reassortment, mutation, and ecological adaptation have facilitated the emergence of novel hantavirus strains with zoonotic potential. Environmental disruption, climate change, urbanization, and increasing human encroachment into wildlife habitats are intensifying spillover risks. Recent concerns regarding Andes virus and potential human-to-human transmission have renewed global attention toward hantavirus pandemic preparedness. This review explores the evolutionary origins, molecular evolution, reservoir dynamics, spillover pathways, mechanisms of human infection, and future pandemic risks associated with hantaviruses. Strategies for surveillance, prevention, and therapeutic development are also discussed.Keywords: Hantavirus, zoonosis, spillover, viral evolution, Andes virus, HFRS, HCPS, reservoir hosts, pandemic potential 1. IntroductionEmerging zoonotic viruses represent one of the greatest threats to global public health in the twenty-first century. Among these pathogens, hantaviruses have gained increasing attention due to their high mortality rates, expanding host range, and growing evidence of ecological adaptation. Hantaviruses are negative-sense single-stranded RNA viruses belonging to the order Bunyavirales and family Hantaviridae (Jonsson et al., 2010).Historically, hantaviruses were primarily associated with rodents, but modern molecular studies have identified genetically diverse hantaviruses in shrews, moles, bats, amphibians, and fish, suggesting ancient evolutionary origins and complex host relationships (Guo et al., 2023). Human infection by hantaviruses can result in two major clinical syndromes:1.Hemorrhagic fever with renal syndrome (HFRS), mainly in Europe and Asia. 2.Hantavirus cardiopulmonary syndrome (HCPS/HPS), mainly in the Americas. Mortality rates range from 5% to over 40% depending on viral strain and healthcare access (Vaheri et al., 2013). Recent outbreaks involving Andes virus have raised concerns about possible human-to-human transmission and the pandemic potential of specific hantavirus lineages. 2. Taxonomy and Genomic Organization of HantavirusesHantaviruses possess a tri-segmented RNA genome composed of:·Large (L) segment encoding RNA-dependent RNA polymerase ·Medium (M) segment encoding envelope glycoproteins Gn and Gc ·Small (S) segment encoding nucleocapsid protein The segmented nature of the genome facilitates genetic reassortment, an important evolutionary mechanism enabling emergence of novel strains (Klempa, 2018). Major pathogenic hantaviruses include:VirusReservoirDiseaseHantaan virusApodemus agrariusHFRSSeoul virusRattus norvegicusHFRSPuumala virusBank voleMild HFRSDobrava-Belgrade virusField miceSevere HFRSSin Nombre virusDeer mouseHCPSAndes virusLong-tailed pygmy rice ratHCPSRecent taxonomic revisions recognize multiple genera and over 50 species within Hantaviridae (Guo et al., 2023). 3. Evolutionary Origins of Hantaviruses3.1 Ancient Origins and Co-EvolutionEarlier theories suggested strict co-evolution between hantaviruses and rodents. However, phylogenetic analyses now indicate a more complicated evolutionary scenario involving both co-divergence and host switching (Yanagihara et al., 2014). The discovery of hantaviruses in insectivorous bats and shrews implies that ancestral hantaviruses may have originated in non-rodent mammals millions of years ago. Molecular clock analyses estimate hantavirus evolution over tens of millions of years (Yanagihara et al., 2014). 3.2 Host SwitchingCross-species transmission has played a major role in hantavirus diversification. Viral adaptation following host switching can lead to emergence of strains capable of infecting humans. Several phylogenetic studies demonstrate incongruence between viral and host phylogenies, supporting repeated host-switching events throughout evolution (Arai et al., 2014). 3.3 Reassortment and Genetic DiversityBecause hantaviruses possess segmented genomes, reassortment between strains may occur during co-infection. Such reassortment can alter virulence, transmissibility, and host specificity (Klempa, 2018). Reassortment has been documented among several hantavirus species and is considered a major driver of evolutionary diversification. 4. Reservoir Hosts and Ecological DynamicsRodents remain the primary reservoirs of pathogenic hantaviruses. Viral persistence within rodent populations usually occurs without causing severe disease, indicating long-term host adaptation.Reservoir species include:·Deer mice ·Cotton rats ·Bank voles ·Norway rats ·Field mice Transmission among rodents occurs through aggressive interactions, saliva exchange, urine contamination, and environmental exposure.Ecological disturbances strongly influence hantavirus epidemiology. Deforestation, climate variability, agricultural expansion, and urbanization alter rodent population dynamics and increase human contact with infected hosts. Climate-driven increases in rainfall can expand food availability, causing rodent population surges and subsequent increases in hantavirus transmission. The 1993 Four Corners outbreak in the United States demonstrated this ecological relationship. 5. Evolutionary Pathways to Human Infection5.1 Spillover TransmissionHuman infection generally occurs through inhalation of aerosolized particles contaminated with rodent urine, feces, or saliva. Additional transmission routes include:·Rodent bites ·Contaminated food ·Direct contact with excreta Spillover events are facilitated by:·Habitat encroachment ·Poor sanitation ·Occupational exposure ·Agricultural activities ·Climate-driven ecological shifts Mathematical models suggest that ecological interfaces between wildlife, intermediate hosts, and humans significantly increase zoonotic emergence risk (Royce & Fu, 2019). 5.2 Viral Adaptation to HumansMost hantaviruses show limited human-to-human transmission. However, Andes virus appears capable of rare interpersonal spread, especially among close contacts. Potential evolutionary adaptations facilitating human infection include:·Enhanced receptor binding ·Immune evasion ·Increased aerosol stability ·Improved replication efficiency in human endothelial cells Mutations affecting viral glycoproteins may alter host tropism and transmission dynamics. 6. Andes Virus and Human-to-Human TransmissionAndes virus (ANDV), endemic to South America, is unique among hantaviruses because it has demonstrated evidence of person-to-person transmission under specific circumstances.Systematic reviews indicate that while evidence remains limited, close-contact transmission is biologically plausible for ANDV (Toledo et al., 2021). Recent reports involving a cruise ship outbreak in 2026 have intensified concerns regarding ANDV transmissibility. Investigations by global health authorities suggest possible limited human-to-human spread among close contacts. Although current evidence does not indicate pandemic-level transmissibility, these outbreaks emphasize the evolutionary potential of hantaviruses and the importance of continuous surveillance. 7. Molecular Mechanisms of PathogenesisHantaviruses primarily target endothelial cells, increasing vascular permeability and causing capillary leakage.Pathogenic mechanisms include:·Dysregulated immune responses ·Cytokine storm ·Endothelial dysfunction ·Platelet abnormalities In HCPS, pulmonary edema and cardiogenic shock dominate clinical presentation, whereas HFRS primarily affects renal function.Mortality rates vary substantially:SyndromeMortality RateMild HFRS<1%Severe HFRS5–15%HCPS30–40%Host immune responses significantly influence disease severity. 8. Global Distribution and Emerging RisksHantaviruses exhibit wide geographic distribution:·Asia: Hantaan and Seoul viruses ·Europe: Puumala and Dobrava viruses ·Americas: Sin Nombre and Andes viruses Globalization, travel, climate change, and wildlife trade may facilitate geographic expansion of reservoir hosts and viral dissemination.Urban rodent-associated Seoul virus infections are increasingly reported worldwide, demonstrating the adaptability of hantaviruses to urban ecosystems (Guo et al., 2023). The increasing frequency of zoonotic outbreaks globally highlights the necessity for integrated “One Health” surveillance systems linking human, animal, and environmental health. 9. Diagnostics, Treatment, and Prevention9.1 DiagnosticsDiagnostic approaches include:·RT-PCR ·ELISA ·Immunofluorescence assays ·Serological testing Early diagnosis remains difficult because initial symptoms resemble influenza-like illnesses.9.2 TreatmentCurrently, no universally approved antiviral therapy exists for hantavirus infection. Treatment remains largely supportive, including:·Oxygen therapy ·Mechanical ventilation ·Hemodynamic stabilization ·Renal support Ribavirin shows partial effectiveness against some Old World hantaviruses when administered early.Recent outbreaks have renewed calls for development of monoclonal antibodies and vaccines targeting hantaviruses. 9.3 PreventionPreventive strategies include:·Rodent control ·Environmental sanitation ·Safe food storage ·Protective equipment for high-risk occupations ·Public awareness campaigns Future prevention will likely require genomic surveillance and predictive ecological modeling. 10. Future Perspectives and Pandemic PotentialHantaviruses possess several chara
Zahid Hussain (Sun,) studied this question.