Rodent Viruses Research Articles

Application of a Sensitive Capture Sequencing Approach to Reservoir Surveillance Detects Novel Viruses in Zambian Wild Rodents

We utilized a pan-viral capture sequencing assay, VirCapSeq-VERT, to assess viral diversity in rodents from the Eastern Province of Zambia as a model for pre-pandemic viral reservoir surveillance. We report rodent adeno-, parvo-, paramyxo-, and picornaviruses that represent novel species or isolates, including murine adenovirus 4, two additional species in the genus Chaphamaparvovirus, two paramyxoviruses distantly related to unclassified viruses in the genus Jeilongvirus, and the first Aichivirus A sequence identified from rodents in Africa. Our results emphasize the importance of rodents as a reservoir for potential zoonotic viruses.

Promotion of order Bunyavirales to class Bunyaviricetes to accommodate a rapidly increasing number of related polyploviricotine viruses.

Prior to 2017, the family Bunyaviridae included five genera of arthropod and rodent viruses with tri-segmented negative-sense RNA genomes related to the Bunyamwera virus. In 2017, the International Committee on Taxonomy of Viruses (ICTV) promoted the family to order Bunyavirales and subsequently greatly expanded its composition by adding multiple families for non-segmented to polysegmented viruses of animals, fungi, plants, and protists. The continued and accelerated discovery of bunyavirals highlighted that an order would not suffice to depict the evolutionary relationships of these viruses. Thus, in April 2024, the order was promoted to class Bunyaviricetes. This class currently includes two major orders, Elliovirales (Cruliviridae, Fimoviridae, Hantaviridae, Peribunyaviridae, Phasmaviridae, Tospoviridae, and Tulasviridae) and Hareavirales (Arenaviridae, Discoviridae, Konkoviridae, Leishbuviridae, Mypoviridae, Nairoviridae, Phenuiviridae, and Wupedeviridae), for hundreds of viruses, many of which are pathogenic for humans and other animals, plants, and fungi.

The discovery of novel variants reveals the genetic diversity and potential origin of Seoul orthohantavirus.

Seoul orthohantavirus (SEOV) has been identified as one of the main causative agents of hemorrhagic fever with renal syndrome (HFRS) in China. The virus was found circulating in rodent populations in almost all provinces of the country, reflecting the wide distribution of HFRS. Here, using the direct immunofluorescence assay (DFA) and real-time quantitative reverse transcription PCR (qRT-PCR) approach, we performed screening in 1784 small mammals belonging to 14 species of three orders captured in the main areas of HFRS endemicity in Yunnan province (southwestern China) and identified 37 SEOV-positive rats (36 Rattus norvegicus and 1 Rattus tanezumi). A 3-year surveillance of HFRS epidemics and dynamics of rodent reservoir density and virus prevalence implied a potential correlation between them. The subsequent meta-transcriptomic sequencing and phylogenetic analyses revealed three SEOV variants, among which two are completely novel. The ancestral character state reconstruction (ACSR) analysis based on both novel variants and documented strains from 5 continents demonstrated that SEOV appeared to originate near the southwestern area (Yunnan-Kweichow Plateau) of China, then could spread to other regions and countries by their rodent carriers, resulting in a global distribution today. In summary, these data furthered the understanding regards genetic diversity and the potential origin for SEOV. However, the expanding endemic foci in the province suggest that the virus is spreading over a wider region and is much more diverse than previous depicted, which means that increased sampling is necessary.

Spread of Puumala Hantavirus to New Areas in a Large Croatian Outbreak of Hemorrhagic Fever with Renal Syndrome, 2021.

Background: The largest documented outbreak of hemorrhagic fever with renal syndrome occurred in Primorje-Gorski Kotar County, Croatia, in 2021, marking the first-time cases of hantavirus infection recorded outside of the known endemic region in the north of the county. Aim: To identify the factors contributing to the spread of the outbreak and to compare risk factors for acquiring hantavirus infection in the endemic and newly affected regions. Methods and Results: A total of 189 cases were confirmed by positive Puumala IgM/IgG antibodies (93.6%), and 13 probable cases were identified by clinical and epidemiological data (6.4%) using a structured questionnaire. Of the 179 cases with available clinical data, 59 (33.0%) were hospitalized. Three cases received hemodialysis, and no deaths were reported. Among 170 cases with information on exposures, 66 (38.8%) reported occupational risk. Cases in the northern part of county were more likely to have been infected in early spring (OR 27.1, 95% CI 2.93-250.7), to report seeing a rodent (OR 6.5; 95%CI 2.3-18.4), and to know someone with hemorrhagic fever with renal syndrome (HFRS) (OR 3.0; 95%CI 1.2-8.0) than cases from the southern part of the county. Data from Croatian Forests Ltd. suggested that an unusually good production of beech seeds in 2020 may have contributed to an increased rodent population in 2021. However, average temperature, rainfall, and humidity data from 2021 did not illustrate a significant difference from previous years (Kruskal-Wallis p = 0.837, p = 0.999, p = 0.108). Conclusion: The 2021 HFRS outbreak was likely fueled by an abundant rodent population and virus transmission in rodent hosts. Human activity, environmental factors, and the ensuing animal-human interactions have spread hantavirus infection from Croatia's mountainous region to a previously nonendemic coastal area with a Mediterranean climate.

Neuregulin-1 reduces necroptosis and protects mice from death caused by respiratory viral infection

Abstract Respiratory syncytial virus (RSV) and influenza type A virus (IAV) cause significant morbidity and mortality even with available vaccines. Pre-existing atopy provides protection against death in mice infected with Sendai virus (SeV), a rodent virus related to RSV. We found neuregulin-1 (NRG1) expressed at high levels in atopic mice, and when given exogenously (500 ng/day i.n for five days) to non-atopic mice provides significant protection against mortality from lethal doses of both SeV (2x106 pfu) and IAV (3x103 pfu PR8-mouse adapted). Further, using well-differentiated human airway epithelial cells, NRG-1 was found to improve epithelial barrier function following RSV infection. RSV has been reported to cause necroptosis, which can induce inflammation and alter epithelial membrane permeability. We hypothesized the survival advantage of NRG1 involves inhibition of necroptosis. Treating cells from the murine airway epithelial cell line LET-1 with NRG1 before inoculation with SeV significantly inhibited viral induced necroptosis as measured by a real-time non-lytic apoptosis/necroptosis assay. Furthermore, NRG1 reduced expression of genes promoting necroptosis (RIPK3 and MLKL) in well-differentiated human bronchial epithelial cells 72h post RSV infection. Together, these data suggest NRG1 modulates viral induced cell death through inhibition of necroptosis of epithelial cells and may explain the reduced airway leak and increased survival seen in our model.

The Prevalence of Tick-Borne Encephalitis Virus in Wild Rodents Captured in Tick-Borne Encephalitis Foci in Highly Endemic Lithuania.

Wild rodents are considered to be one of the most important TBEV-amplifying reservoir hosts; therefore, they may be suitable for foci detection studies. To investigate the effectiveness of viral RNA detection in wild rodents for suspected TBEV foci confirmation, we trapped small rodents (n = 139) in various locations in Lithuania where TBEV was previously detected in questing ticks. Murine neuroblastoma Neuro-2a cells were inoculated with each rodent sample to maximize the chances of detecting viral RNA in rodent samples. TBEV RNA was detected in 74.8% (CI 95% 66.7-81.1) of the brain and/or internal organ mix suspensions, and the prevalence rate increased significantly following sample cultivation in Neuro-2a cells. Moreover, a strong correlation (r = 0.88; p < 0.05) was found between the average monthly air temperature of rodent trapping and the TBEV RNA prevalence rate in cell culture isolates of rodent suspensions, which were PCR-negative before cultivation in cell culture. This study shows that wild rodents are suitable sentinel animals to confirm TBEV foci. In addition, the study results demonstrate that sample cultivation in cell culture is a highly efficient method for increasing TBEV viral load to detectable quantities.

Molecular detection of monkeypox virus in wild rodents and humans in Ibadan, Nigeria - a cross-sectional study

Molecular detection of monkeypox virus in wild rodents and humans in Ibadan, Nigeria - a cross-sectional study

RNA virus diversity in rodents.

Many zoonotic disease emergencies are associated with RNA viruses in rodents that substantially impact public health. With the widespread application of meta-genomics and meta-transcriptomics for virus discovery over the last decade, viral sequences deposited in public databases have expanded rapidly, and the number of novel viruses discovered in rodents has increased. As important reservoirs of zoonotic viruses, rodents have attracted increasing attention for the risk of potential spillover of rodent-borne viruses. However, knowledge of rodent viral diversity and the major factors contributing to the risk of zoonotic epidemic outbreaks remains limited. Therefore, this study analyzes the diversity and composition of rodent RNA viruses using virus records from the Database of Rodent-associated Viruses (DRodVir/ZOVER), which covers the published literatures and records in GenBank database, reviews the main rodent RNA virus-induced human infectious diseases, and discusses potential challenges in this field.

Filling the gaps in the Argentinian distribution of orthohantavirus: First finding of Lechiguanas virus in rodents from Corrientes, Argentina.

Hantavirus Pulmonary Syndrome (HPS) is an emerging infectious disease caused by orthohantaviruses in the Americas. In Argentina, since 1995, several reservoirs and virus variants have been described, but the northeastern and central endemic zones in the country include an area without human or rodent infections, despite sharing rodent species with areas with that disease. The aim of this study was to search for orthohantavirus in rodent communities that inhabit this area, which borders two endemic areas of HPS. Small rodents were captured in June of 2022 through a total effort of 644 trap nights distributed in five grids located in the Iberá National Park, Corrientes, Northeastern Argentina. All rodents were sexed, weighed, and the species was recorded. Blood samples were extracted to detect ANDV-specific immunoglobulin G (IgG), and to extract the RNA virus. Trimmed sequences were mapped against reference sequences from GenBank. We captured a total of 36 Oligoryzomys flavescens and 15 Oxymycterus rufus. We detected the O. flavescens species infected with Lechiguanas orthohantavirus in the camping area of the National Park. A nucleotide comparison with previously published sequences shows a 98.34% similarity to the virus obtained from a human case of HPS reported in the adjacent Misiones province. This study demonstrated, for the first time, that O. flavescens is a host of the Lechiguanas orthohantavirus in this zone and contributes to closing information gaps on the distribution of orthohantavirus in Argentina. Additionally, the high similarity with the hantavirus found in the human case of Misiones suggests that the reservoir in that province would also be O. flavescens (not previously confirmed). This information permits us to focus on the preventive measurements to protect the human population.

Metagenomics screening of viruses in Arusha, north Tanzania: a one health perspective across wild rodents, domestic dogs and humans

Background: One of the most significant and perilous challenges faced by African societies, including Tanzania, is the public health threat posed by zoonotic viruses. This study aimed to ascertain the presence of viruses in wild rodents, domestic dogs, and humans who shared the same environment. Methods: A cross-sectional study was conducted in the Ngorongoro district from January to September 2022. Metagenomics next-generation sequencing technologies, including Illumina (MiSeq) and Oxford Nanopore (MinION), were employed to identify viruses in 530 blood samples collected from 200 humans, 230 wild rodents, and 100 domestic dogs. The captured wild rodents belonged to various species: Mastomys spp (n=87), Ratus spp (n=45), Avicanthis spp (n=40), Arcomys spp (n=28), Mus spp (n=16), and Field mice (n=14). The taxonomic classification of viruses was carried out using the Kraken2 program. Results: A total of 20 RNA and 20 DNA viral families were detected. Zoonotic RNA families identified in rodents included Peribunyaviridae, Hantaviridae, Flaviviridae, Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Retroviridae, Picornaviridae, Arenaviridae, Togaviridae, and Tobaniviridae. The zoonotic DNA families detected in rodents were Adenoviridae, Poxviridae, Herpesviridae, Anelloviridae, and Circoviridae. Peribunyaviridae and Hataviridae were identified in both humans and rodents. Unclassified +ssRNA viruses were found in dogs and humans. Herpesviridae was present in all three hosts. When compared to dogs and humans, rodents harbored zoonotic viruses that pose a significant public health safety concern. Conclusion: The study unveiled a noteworthy pattern where the majority of RNA and DNA viruses with zoonotic potential were detected in wild rodents, as opposed to dogs and humans. These findings underscore the pivotal role played by wild rodent populations in the transmission and maintenance of such viruses.

Winter is coming-The role of seasonality through the lens of the rodent virome.

Rodent virus communities (viromes) are overrepresented with zoonotic viruses, and as such are a key host system for the study of zoonotic viruses. However, the extent of viral diversity beyond characterized zoonotic viruses, and the factors that modulate the viromes of rodents remain opaque. In this issue of Molecular Ecology, Raghwani et al. (2023) use rodents as a model to understand the role of seasonality in dictating virome abundance and composition-a factor known to play an important role in most animal one-host, one-pathogen systems. These data are not only highly relevant to rodents, but have broad applications across understanding and disentangling animal virome ecology.

Current State of the Issue of Hemorrhagic Fever with Renal Syndrome in the Rostov Region

Hemorrhagic fever with renal syndrome (HFRS) is registered in various geographical regions of the Russian Federation and occupies one of the leading positions among natural-focal human diseases in Russia. The aim of the study was to assess the epidemiological situation on HFRS in the Rostov Region. Materials and methods. Laboratory diagnostics of field material (samples from wild rodents) for the presence of antigens of HFRS pathogens and screening of blood sera from donors, residents of the region, for the presence of class G antibodies to viruses that cause HFRS were carried out by enzyme immunoassay during 2020 and 2021. Results and discussion. Hantavirus antigens were identified in five administrative districts of the Region in 2020, infection with HFRS virus in small mouse-like rodents was 7.1 %. In 2021, spontaneous infection of carriers was detected in 2.8 % of the samples, found in four districts of the Region. The presence of the virus markers was recorded in populations of five species of mouse-like rodents: house mouse, wood mouse, common vole, small wood mouse, yellow-bellied mouse. Among healthy population, class G antibodies were registered in 6.8 % in the surveyed territories in 2020, and 4.5 % in 2021. Detection of virus markers in carriers and the presence of a natural immune layer of the population as regards HFRS agents suggest the existence of a natural HFRS focus in the Rostov Region.

Using archived and biocollection samples towards deciphering the DNA virus diversity associated with rodent species in the families cricetidae and heteromyidae

Rodentia is the most speciose order of mammals, and they are known to harbor a wide range of viruses. Although there has been significant research on zoonotic viruses in rodents, research on the diversity of other viruses has been limited, especially for rodents in the families Cricetidae and Heteromyidae. In fecal and liver samples of nine species of rodents, we identify 346 distinct circular DNA viral genomes. Of these, a large portion are circular, single-stranded DNA viruses in the families Anelloviridae (n = 3), Circoviridae (n = 5), Genomoviridae (n = 7), Microviridae (n = 297), Naryaviridae (n = 4), Vilyaviridae (n = 15) and in the phylum Cressdnaviricota (n = 13) that cannot be assigned established families. We also identified two large bacteriophages of 36 and 50 kb that are part of the class Caudoviricetes. Some of these viruses are clearly those that infect rodents, however, most of these likely infect various organisms associated with rodents, their environment or their diet.

The ecology of viruses in urban rodents with a focus on SARS-CoV-2

ABSTRACT Wild animals are naturally infected with a range of viruses, some of which may be zoonotic. During the human COVID pandemic there was also the possibility of rodents acquiring SARS-CoV-2 from people, so-called reverse zoonoses. To investigate this, we sampled rats (Rattus norvegicus) and mice (Apodemus sylvaticus) from urban environments in 2020 during the human COVID-19 pandemic. We metagenomically sequenced lung and gut tissue and faeces for viruses, PCR screened for SARS-CoV-2, and serologically surveyed for anti-SARS-CoV-2 Spike antibodies. We describe the range of viruses that we found in these two rodent species. We found no molecular evidence of SARS-CoV-2 infection, though in rats we found lung antibody responses and evidence of neutralization ability that are consistent with rats being exposed to SARS-CoV-2 and/or exposed to other viruses that result in cross-reactive antibodies.

Neuregulin-1 reduces vascular leak and airway epithelium permeability caused by respiratory viral infection

Abstract Respiratory viruses, such as Respiratory Syncytial Virus (RSV), are associated with significant morbidity and mortality. Mice with pre-existing atopy are protected from mortality to Sendai virus (SeV), a rodent virus related to RSV. We found that lungs of atopic mice had increased levels of neuregulin-1(NRG1), and hypothesized that SeV induces death via lung vascular leak, and that NRG1 might inhibit vascular leakage. Non-atopic C57Bl/6 mice were treated with NRG1 (500ng/30 mcl, i.n) or PBS for five days before infection with SeV (2×10 5pfu) or UV-inactivated SeV (UV-SeV) and 8 days post viral inoculation, Evan’s Blue Dye (EBD) was injected i.v with EBD concentration determined spectrophotometrically one hour later in homogenized lungs. Vascular leak in SeV-infected mice was 65.25% and 46.62% more than in UV-SeV-treated or SeV-infected mice pre-treated with NRG1, respectively. We also found that RSV infection of well-differentiated human bronchial epithelial cells (hBEC) grown at the air-liquid interface caused 70KDa FITC-Dextran leakage 8 days post-inoculation. NRG1 pretreatment for 5 days before RSV inoculation reduced epithelial leakage 8 days post-inoculation by 2.5 fold (p&amp;lt;0.001). These results suggest NRG1 has the potential to improve epithelial barrier function in rodent and human systems and may explain the increased survival following a severe respiratory viral infection. Abigail Wexner Research Institute at Nationwide Children’s Hospital, Start-up fund to MHG

Emergence and History

Emergence and History

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.

Potentially Zoonotic Viruses in Wild Rodents, United Arab Emirates, 2019—A Pilot Study

The majority of emerging viral infectious diseases in humans originate from wildlife reservoirs, such as rodents and bats. We investigated a possible reservoir, namely wild gerbils and mice trapped in a desert reserve within the emirate of Dubai, United Arab Emirates (UAE). In total, 52 gerbils and 1 jird (Gerbillinae), 10 house mice (Mus musculus), and 1 Arabian spiny mouse (Acomys dimidiatus) were sampled. Oro-pharyngeal swabs, fecal samples, attached ticks, and organ samples (where available) were screened by (RT-q)PCR for the following viruses: Middle East respiratory syndrome-related coronavirus, Crimean-Congo hemorrhagic fever orthonairovirus, Alkhumra hemorrhagic fever virus, hantaviruses, Lymphocytic choriomeningitis mammarenavirus, Rustrela virus, poxviruses, flaviviruses, and herpesviruses. All of the samples were negative for all investigated viruses, except for herpesviruses: 19 gerbils (35.8%) and seven house mice (70.0%) were positive. The resulting sequences were only partly identical to sequences in GenBank. Phylogenetic analysis revealed three novel betaherpesviruses and four novel gammaherpesviruses. Interestingly, species identification of the positive gerbils resulted in eight individuals clustering in a separate clade, most closely related to Dipodillus campestris, the North African gerbil, indicating either the expansion of the geographic range of this species, or the existence of a closely related, yet undiscovered species in the UAE. In conclusion, we could not find evidence of persistence or shedding of potentially zoonotic viruses in the investigated rodent cohorts of limited sample size.

First study of Seoul virus (SEOV) in urban rodents from newly urbanized areas of Gran La Plata, Argentina

Alterations of ecosystems have deep effects on the distribution of parasites. Big cities of Argentina present structural features that favor the presence of synanthropic species, acting as source of zoonotic diseases, for example in urban rodents: the Norway rat (Rattus norvegicus) and the black rat (R. rattus). One of the important zoonotic pathogens related are the RNA virus Hantavirus, with high prevalence rates in South America. The aim of this study was to explore and identify the presence of Hantavirus in urban rodents from Gran La Plata, Argentina. The presence of anti-hantavirus IgG antibodies was determined by the Enzyme-Linked Immunosorbent Assay. Six samples turned out positive for Seoul virus (SEOV, p = 14.3%). These are the first records of SEOV in urban rodents in Gran La Plata. It represents the first report in R. rattus in Argentina, and in America. This situation underscores the inequality and historical forgetfulness of a portion of society, calling for urgent action to be taken in this regard.

Global Comprehensive Outlook of Hantavirus Contagion on Humans: A Review.

Hantaviruses are rodent viruses that have been identified as etiologic agents of 2 diseases in humans: Hemorrhagic Fever with Renal Syndrome (HFRS) and Nephropathiaepidemica (NE) in the Old World and Hantavirus Pulmonary Syndrome (HPS) in the New World. Orthohantavirus is a genus of single-stranded, enveloped, negative-sense RNA viruses in the family Hantaviridae of the order Bunyavirales. The important reservoir of Hantaviruses is rodents. Each virus serotype has its unique rodent host species and is transmitted to human beings with the aid of aerosolized virus, which is shed in urine, faeces and saliva and hardly by a bite of the contaminated host. Andes virus is the only Hantavirus identified to be transmitted from human-to-human and its major signs and symptoms include fever, headache, muscle aches, lungs filled with fluid, etc. In early 1993, this viral syndrome appeared in the Four Corner location in the southwestern United States. The only accepted therapeutics for this virus is Ribavirin. Recently, serological examinations to identify Hantavirus antibodies have become most popular for investigation among humans and rodent reservoirs.