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The number of documented American orthohantaviruses has increased significantly over recent decades, but most fundamental research has remained focused on just two of them: Andes virus (ANDV) and Sin Nombre virus (SNV). The majority of American orthohantaviruses are known to cause disease in humans, and most of these pathogenic strains were not described prior to human cases, indicating the importance of understanding all members of the virus clade. In this review, we summarize information on the ecology of under-studied rodent-borne American orthohantaviruses to form general conclusions and highlight important gaps in knowledge. Information regarding the presence and genetic diversity of many orthohantaviruses throughout the distributional range of their hosts is minimal and would significantly benefit from virus isolations to indicate a reservoir role. Additionally, few studies have investigated the mechanisms underlying transmission routes and factors affecting the environmental persistence of orthohantaviruses, limiting our understanding of factors driving prevalence fluctuations. As landscapes continue to change, host ranges and human exposure to orthohantaviruses likely will as well. Research on the ecology of neglected orthohantaviruses is necessary for understanding both current and future threats to human health. 

Abstract As anthropogenic factors continue to degrade natural areas, habitat management is needed to restore and maintain biodiversity. However, the impacts of different habitat management regimes on ecosystems have largely focused on vegetation analyses, with limited evaluation of downstream effects on wildlife. We compared the effects of grassland management regimes (prescribed burning, cutting/haying, or no active management) on rodent communities and the viruses they hosted. Rodents were trapped in 13 existing grassland sites in Northwest Arkansas, USA during 2020 and 2021. Rodent blood samples were screened for antibodies against three common rodent‐borne virus groups: orthohantaviruses, arenaviruses, and orthopoxviruses. We captured 616 rodents across 5953 trap nights. Burned and unmanaged sites had similarly high abundance and diversity, but burned sites had a higher proportion of grassland species than unmanaged sites; cut sites had the highest proportion of grassland species but the lowest rodent abundance and diversity. A total of 38 rodents were seropositive for one of the three virus groups (34 orthohantavirus, three arenavirus, and one orthopoxvirus). Thirty‐six seropositive individuals were found in burned sites, and two orthohantavirus‐seropositive individuals were found in cut sites. Cotton rats and prairie voles, two grassland species, accounted for 97% of the rodents seropositive for orthohantavirus. Our study indicates that prescribed burns lead to a diverse and abundant community of grassland rodent species compared with other management regimes; as keystone taxa, these results also have important implications for many other species in food webs. Higher prevalence of antibodies against rodent‐borne viruses in burned prairies shows an unexpected consequence likely resulting from robust host population densities supported by the increased habitat quality of these sites. Ultimately, these results provide empirical evidence that can inform grassland restoration and ongoing management strategies. 

Orthohantaviruses are globally emerging zoonotic pathogens. While the reservoir host role of several rodent species is well-established, detailed research on the mechanisms of host-othohantavirus interactions has been constrained by the lack of an experimental system that is able to effectively replicate natural infections in controlled settings. Here we report the isolation, and genetic and phenotypic characterization of a novel Puumala orthohantavirus (PUUV) in cells derived from its reservoir host, the bank vole. The isolation process resulted in cell culture infection that evaded antiviral responses, persisted cell passaging, and had minor viral genome alterations. Critically, experimental infections of bank voles with the new isolate resembled natural infections in terms of viral load and host cell distribution. When compared to an attenuated Vero E6 cell-adapted PUUV Kazan strain, the novel isolate demonstrated delayed virus-specific humoral responses. A lack of virus-specific antibodies was also observed during experimental infections with wild-type PUUV, suggesting that delayed seroconversion could be a general phenomenon during orthohantavirus infection in reservoir hosts. Our results demonstrate that orthohantavirus isolation on cells derived from a vole reservoir host retains wild-type infection properties and should be considered the method of choice for experimental infection models to replicate natural processes. 

In the light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programmes will identify hundreds of novel viruses that might someday pose a threat to humans. To support the extensive task of laboratory characterization, scientists may increasingly rely on data-driven rubrics or machine learning models that learn from known zoonoses to identify which animal pathogens could someday pose a threat to global health. We synthesize the findings of an interdisciplinary workshop on zoonotic risk technologies to answer the following questions. What are the prerequisites, in terms of open data, equity and interdisciplinary collaboration, to the development and application of those tools? What effect could the technology have on global health? Who would control that technology, who would have access to it and who would benefit from it? Would it improve pandemic prevention? Could it create new challenges? This article is part of the theme issue ‘Infectious disease macroecology: parasite diversity and dynamics across the globe’.