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Hantaviridae currently encompasses seven genera and 53 species. Multiple hantaviruses such as Hantaan virus, Seoul virus, Dobrava-Belgrade virus, Puumala virus, Andes virus, and Sin Nombre virus are highly pathogenic to humans. They cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome or hantavirus pulmonary syndrome (HCPS/HPS) in many countries. Some hantaviruses infect wild or domestic animals without causing severe symptoms. Rodents, shrews, and bats are reservoirs of various mammalian hantaviruses. Recent years have witnessed significant advancements in the study of hantaviruses including genomics, taxonomy, evolution, replication, transmission, pathogenicity, control, and patient treatment. Additionally, new hantaviruses infecting bats, rodents, shrews, amphibians, and fish have been identified. This review compiles these advancements to aid researchers and the public in better recognizing this zoonotic virus family with global public health significance.

To explore hantavirus infection patterns in Latin America, we conducted molecular and serologic hantavirus investigations among 3,400 febrile patients from Peru during 2020-2021. Reverse transcription PCR indicated that a patient from Loreto, in the Peruvian Amazon, was positive for Rio Mamore hantavirus (serum, 3.8 × 10 copies/mL). High genomic sequence identity of 87.0%-94.8% and phylogenetic common ancestry with a rodent-associated Rio Mamore hantavirus from Loreto in 1996 indicated endemicity. In 832 samples from Loreto, hantavirus incidence based on IgM ELISA of pooled Sin Nombre (SNV) and Andes virus (ANDV) nucleoproteins and immunofluorescence assay-based end-point titration using SNV/ANDV/Hantaan/Puumala/Saarema/Dobrava/Seoul hantaviruses was 0.5%. Across 3 ecologically distinct departments in Peru, SNV/ANDV IgG ELISA/IFA-based reactivity was 1.7%, suggesting circulation of antigenically distinct New World hantaviruses. Testing for arboviruses, nonendemic pathogens, and antigen-free ELISA corroborated nonspecific reactivity in 2 IgG and several IgM ELISA-positive serum samples. Hantavirus diagnostics and surveillance should be strengthened in Peru ad across Latin America.

Orthohantaviruses are zoonotic pathogens that cause acute and severe syndromes in humans. This review was performed to estimate the occurrence of human orthohantaviruses in South America between 2010 and 2022. A careful evaluation of the eligibility and quality of the articles was carried out after a systematic bibliographic search of four databases. The pooled frequency of human orthohantaviruses was calculated using a random effects model meta-analysis. The heterogeneity of estimates (resulting from the chi2 test and I2 statistics) was investigated by subgroup analysis and meta-regression. 1,962 confirmed cases of orthohantavirus infections were diagnosed among 35,548 individuals from seven South American countries. The general occurrence of orthohantaviruses was estimated to be 4.4% (95% confidence interval: 2.9–6.2%) based on general pooling of human cases from 32 studies. In a subgroup analysis considering the study design and method of diagnosis, the percentages of diagnosed orthohantavirus infections differed substantially (I2 = 97.8%, p = 0.00) among South American countries. Four genetic variants of orthohantavirus have been identified circulating in Argentina, Brazil, Bolivia, Chile, Colombia, and Peru. Although laboratory diagnosis of orthohantaviruses is not performed in many countries in South America, there is evidence that four different orthohantaviruses are circulating in the region. The pooled occurrence of viral infection was approximately 4.0% in more than half of the South American countries. Updated information on the occurrence of human infections is essential for monitoring the territorial spread and determining the frequency of this zoonosis.

Background Eurasian pathogenic orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) characterized by acute kidney injury (AKI). The virulence of orthohantaviruses varies enormously and direct infection of different renal cell types contribute to pathogenesis. Glomerular mesangial cells play an essential role in the interplay between kidney cells and proper kidney function. Therefore, we analyzed the replication competence of different orthohantavirus species in primary mesangial cells and a mesangial cell line. Methods We tested the suitability of the mesangial cell line CIHGM-1 (conditionally immortalized human glomerular mesangial cells) as cell culture model for orthohantavirus kidney infection by comparison with primary human renal mesangial cells (HRMCs). We analyzed infection with high pathogenic Hantaan virus (HTNV), moderate pathogenic Puumala virus (PUUV) and non-/low-pathogenic Tula virus (TULV). Results Effective viral spread was observed for PUUV only, whereas infection with HTNV and TULV was abortive. However, in contrast to TULV, HTNV exhibits an initially high infection rate and declines afterwards. This replication pattern was observed in HRMCs and CIHGM-1 cells. Viability or adhesion was neither impaired for PUUV-infected CIHGM-1 nor HRMCs. A loss of migration capacity was observed in PUUV-infected CIHGM-1 cells, but not in HRMCs. Conclusions The identification of differences in the replication competence of pathogenic orthohantavirus strains in renal mesangial cells is of special interest and may provide useful insights in the virus-specific mechanisms of orthohantavirus induced AKI. The use of CIHGM-1 cells will facilitate the research in a relevant cell culture system.

Few cases of hantavirus pulmonary syndrome have been reported in northeastern Argentina. However, neighboring areas show a higher incidence, suggesting underreporting. We evaluated the presence of antibodies against orthohantavirus in small rodents throughout Misiones province. Infected Akodon affinis montensis and Oligoryzomys nigripes native rodents were found in protected areas of Misiones.

During 2020-2023, we sequenced Bayou virus from 2 patients in Louisiana, USA, with hantavirus cardiopulmonary syndrome. Direct virus sequencing demonstrated an inferred evolutionary relationship to previous cases. Our findings demonstrate that separate virus spillovers cause isolated cases and probable wide distribution of Bayou hantavirus in rodents across Louisiana.

On November 2, 2018, a person-to-person transmission outbreak of Andes virus ( Orthohantavirus andesense) began in the small town of Epuyén, Argentina. The strain demonstrated a high capacity for sustained transmission among the human population requiring the implementation of quarantine measures, rigorous contact tracing, isolation of close contacts, and active clinical monitoring to prevent further spread. In this study, we report the isolation of this strain, which we name the ARG-Epuyén strain, directly from a clinical sample after just three passages in cell culture. Complete sequencing revealed only a single amino acid change post-isolation, suggesting that this strain can be considered a non-adapted wild-type Andes virus, marking a critical step toward the development of medical countermeasures against this emerging pathogen. The pathogenicity and transmissibility potential of ARG-Epuyén were evaluated in hamsters, the only animal model for Hantavirus Pulmonary Syndrome. Additionally, this strain was compared with Andes/ARG, an ANDV strain previously isolated from the same geographical area in the Argentinian Patagonia, from a rodent specimen. Our findings revealed high infectiousness and efficient hamster-to-hamster transmission through direct contact experiments, although ARG-Epuyén appeared to be less pathogenic than Andes/ARG.

To further understanding of the structure and morphology of the Orthohantavirus, family Hantaviridae, we have employed cryo-electron microscopy (cryo-EM) for three New World hantaviruses: Andes (ANDV), Sin Nombre (SNV), and Black Creek Canal (BCCV). Building upon our prior cryo-EM and cryo-tomography study of the Old World hantavirus, Hantaan virus (HTNV), we have expanded our studies to examine the entire virion population present in cell culture supernatant. Hence, in contrast to the prior cryo-EM/ET studies in which we used a polyethylene precipitation, a sucrose gradient, and a sucrose cushion, we used two sucrose cushions. We inactivated the material after the first cushion. We tested the method using HTNV which has a known cryo-EM structure and observed equivalent results. Therefore, we used this method to assess the particle distribution of the New World hantaviruses by cryo-EM. Cryo-EM images showed a diverse range of sizes and morphologies for the New World viruses that we classified as round, tubular, and irregular. Strikingly, BCCV virions were mostly tubular. These first cryo-EM images of the New World Orthohantavirus confirm prior EM observations that noted tubular projections of SNV at the plasma membrane during virion morphogenesis but were not confirmed. These findings underscore the need for further investigation of virion morphogenesis of the Orthohantavirus.

Orthohantavirus infection is a zoonotic disease transmitted to humans through contact with infected rodents. In Eurasia, Old World Orthohantaviruses can cause haemorrhagic fever with renal syndrome (HFRS), while in the Americas, New World Orthohantaviruses are responsible for hantavirus cardiopulmonary syndrome (HCPS). In Kazakhstan, the first recorded cases of HFRS appeared in the West Kazakhstan region in 2000, which has since then been established as an endemic area due to the presence of stable rodent reservoirs and recurring human infections. Routine diagnosis of HFRS in this region relies primarily on immunoassays. To enhance diagnostic precision, we aimed to implement both serological and molecular methods on samples from suspected HFRS cases in the endemic West Kazakhstan region and non-endemic Almaty City. A total of 139 paired serum, saliva, and urine samples were analysed using IgM/IgG ELISA, immunoblot assays, and qPCR. Our findings confirm that suspected HFRS cases in West Kazakhstan are associated with the Puumala virus serotype.

Orthohantavirus hantanense (HTNV) poses a substantial global public health threat due to its role in causing hemorrhagic fever with renal syndrome (HFRS). HTNV outbreaks are particularly prevalent in the Gyeonggi and Gangwon Provinces of the Republic of Korea (ROK). This study aimed to evaluate the application of advanced nanopore sequencing and bioinformatics to generate complete genome sequences of HTNV, with the objective of accurately identifying infection sources and analyzing their genetic diversity. In 2022 and 2023, we collected 579 small mammals from 11 distinct locations across Gyeonggi and Gangwon Provinces, as well as in Gwangju Metropolitan City, ROK. Among these, 498 Apodemus agrarius specimens were subjected to an epidemiological survey to investigate HTNV infections. The serological and molecular positivity of HTNV were found to be 65/498 (13.1%) and 17/65 (26.2%), respectively. Furthermore, 15 whole-genome sequences of HTNV were obtained from rodents in Gyeonggi and Gangwon Provinces. We developed a novel amplicon-based nanopore sequencing approach to acquire high-fidelity and precise genomic sequences of HTNV. Genome exchange analysis revealed three reassortant candidates, including heterogeneous L segments, from Paju-si and Yeoncheon-gun in Gyeonggi Province. Our findings enhance the resolution of the spatiotemporal genomic surveillance of HTNV by consistently providing new viral sequences and epidemiological data from HFRS-endemic regions in the ROK. This report signifies a notable advancement in nanopore sequencing techniques and bioinformatics, offering a robust platform for genome-based diagnostics and sophisticated phylogenetic analyses of orthohantaviruses, which are essential for public health strategies aimed at controlling HFRS.