Novel Ozark Orthohantavirus in Hispid Cotton Rats (Sigmodon hispidus), Arkansas, USA.

We report a novel orthohantavirus, putatively named Ozark orthohantavirus, in hispid cotton rats captured within the Ozark Plateau in Arkansas, USA. This virus phylogenetically clusters with other orthohantaviruses that cause severe human disease. Continued orthohantavirus surveillance and virus sequencing are needed to address the potential public health threat of this virus.

Virus isolation data improve host predictions for New World rodent orthohantaviruses.

Identifying reservoir host species is crucial for understanding the ecology of multi-host pathogens and predicting risks of pathogen spillover from wildlife to people. Predictive models are increasingly used for identifying ecological traits and prioritizing surveillance of likely zoonotic reservoirs, but these often employ different types of evidence for establishing host associations. Comparisons between models with different infection evidence are necessary to guide inferences about the trait profiles of likely hosts and identify which hosts and geographical regions are likely sources of spillover. Here, we use New World rodent-orthohantavirus associations to explore differences in the performance and predictions of models trained on two types of evidence for infection and onward transmission: RT-PCR and live virus isolation data, representing active infections versus host competence, respectively. Orthohantaviruses are primarily carried by muroid rodents and cause the diseases haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) in humans. We show that although boosted regression tree (BRT) models trained on RT-PCR and live virus isolation data both performed well and capture generally similar trait profiles, rodent phylogeny influenced previously collected RT-PCR data, and BRTs using virus isolation data displayed a narrower list of predicted reservoirs than those using RT-PCR data. BRT models trained on RT-PCR data identified 138 undiscovered hosts and virus isolation models identified 92 undiscovered hosts, with 27 undiscovered hosts identified by both models. Distributions of predicted hosts were concentrated in several different regions for each model, with large discrepancies between evidence types. As a form of validation, virus isolation models independently predicted several orthohantavirus-rodent host associations that had been previously identified through empirical research using RT-PCR. Our model predictions provide a priority list of species and locations for future orthohantavirus sampling. More broadly, these results demonstrate the value of multiple data types for predicting zoonotic pathogen hosts. These methods can be applied across a range of systems to improve our understanding of pathogen maintenance and increase efficiency of pathogen surveillance.

A framework for understanding and predicting orthohantavirus functional traits.

Orthohantaviruses present a global public health threat; there are 58 distinct viruses currently recognized and case fatality of pathogenic orthohantaviruses ranges from <0.1% to 50%. An Old World versus New World dichotomy is frequently applied to distinguish human diseases caused by orthohantaviruses. However, this geographic grouping masks the importance of phylogeny and virus-host ecology in shaping orthohantavirus traits, especially since related arvicoline rodents and their orthohantaviruses are found in both regions. We argue that orthohantaviruses can be separated into three phylogenetically based rodent host groups with differences in key functional traits, including human disease, transmission route, and virus-host fidelity. This framework can help understand and predict traits of under-studied and newly discovered orthohantaviruses and guide public health and biosafety policy.

Effects of habitat management on rodent diversity, abundance, and virus infection dynamics.

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.

Ecology of Neglected Rodent-Borne American Orthohantaviruses.

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.