Renal Syndrome Research Articles

Various Organ Damages in Rats with Fetal Growth Restriction and Their Slight Attenuation by Bifidobacterium breve Supplementation.

Children with fetal growth restriction (FGR) and its resultant low birthweight (LBW) are at a higher risk of developing various health problems later in life, including renal diseases, metabolic syndrome, and sarcopenia. The mechanism through which LBW caused by intrauterine hypoperfusion leads to these health problems has not been properly investigated. Oral supplementation with probiotics is expected to reduce these risks in children. In the present study, rat pups born with FGR-LBW after mild intrauterine hypoperfusion were supplemented with either Bifidobacterium breve (B. breve) or a vehicle from postnatal day 1 (P1) to P21. Splanchnic organs and skeletal muscles were evaluated at six weeks of age. Compared with the sham group, the LBW-vehicle group presented significant changes as follows: overgrowth from infancy to childhood; lighter weight of the liver, kidneys, and gastrocnemius and plantaris muscles; reduced height of villi in the ileum; and increased depth of crypts in the jejunum. Some of these changes were milder in the LBW-B.breve group. In conclusion, this rat model could be useful for investigating the mechanisms of how FGR-LBW leads to future health problems and for developing interventions for these problems. Supplementation with B. breve in early life may modestly attenuate these problems.

Aspartate aminotransferase to platelet ratio at admission can predict the prognosis of patients with hemorrhagic fever with renal syndrome.

Early indicators are needed to predict the prognosis of patients with hemorrhagic fever with renal syndrome (HFRS). Aspartate aminotransferase to platelet ratio index (APRI) has been shown to be related to mortality risk of patients with various diseases. This study evaluated the prognostic value of APRI and other inflammatory scores in HFRS patients. Data of hospitalized HFRS patients from a tertiary hospital in northwest China were collected and the inflammatory scores such as APRI and neutrophil to lymphocyte count ratio (NLR) were calculated at the day of patient admission. Independent factors related to the survival of patients were determined by multivariate logistic regression. Receiver operating characteristic curve was used to analyze the predictive value, and area under the curve (AUC) and 95% confidence interval (CI) were calculated for quantification. Of the 317 HFRS patients included in study, 15 patients died. Age (OR: 1.10, 95%CI: 1.04-1.16, p = 0.001), NLR (OR: 1.11, 95%CI: 1.02-1.19, p = 0.01), and APRI (OR: 1.06, 95%CI: 1.03-1.10, p = 0.001) were quantitative objective factors independently associated with the survival of patients. APRI had an AUC of 0.95 (95% CI: 0.91-1.00, p < 0.001) for predicting the prognosis of patients, with a sensitivity of 93.3% and a specificity of 86.8%. The performance of APRI was better than that of age or NLR. Patients with an APRI ≥ 6.15 had significantly decreased survival compared with those with an APRI < 6.15. In conclusion, this simple index APRI calculated at admission can serve as a biomarker to identify HFRS patients at risk of poor prognosis.

Genetic diversity and molecular evolution of Seoul virus in Hebei province, China.

Seoul virus (SEOV) is a major pathogen which causes hemorrhagic fever with renal syndrome (HFRS), and is present all over the world. However, there are currently few long-term systematic studies of SEOV's phylogenetic and evolutionary mechanisms in epidemic areas. Thus, in this study, we used RT-PCR combined with NGS to obtain the genomes of six SEOV viruses from 1993, as well as 56 Hebei province-specific tissue samples from 1999 to 2022. Phylogenetic analysis showed that the SEOV samples could be divided into seven groups and showed geographic clustering. The geographic region may be the main factor affecting the genetic diversity of SEOV. We also found that SEOV was subject to strong overall purifying selection and positive selection at certain sites during evolution. Recombination events and high nucleotide substitution rates were also shown to accelerate SEOV's evolution. Evolutionary feature of the L segment is more representative of complete genome. Our detailed analysis provides a deeper understanding of the genetic diversity and evolutionary drivers of SEOV within its primary epidemic areas. It will be important to further monitor epidemiological trends and drivers of variation to help increase our understanding of the pathogenicity of SEOV infections.

Diverse ultrasound image features of unilateral genital tract obstruction with ipsilateral renal anomaly syndrome on genitourinary system segmental sequential ultrasound screening and the accuracy of ultrasonic diagnosis.

Unilateral genital tract obstruction with ipsilateral renal anomaly (UGTOIRA) syndrome is a rare congenital urogenital anomaly, characterized by different combinations of uterine abnormalities, unilateral cervical-vaginal obstruction, and ipsilateral renal abnormalities. Timely and correct diagnosis is critical. In this study, we analyzed the diverse ultrasound image features of UGTOIRA syndrome on genitourinary system segmental sequential ultrasound screening (SSUS) and the accuracy of ultrasonic diagnosis. The data from 59 patients with UGTOIRA syndrome over the last decade were analyzed retrospectively, which included ultrasound presentations and diagnoses of abnormalities of the uterus, cervix, and vagina, as well as the conditions associated with the bilateral fallopian tubes, ovaries, pelvis, kidneys and ureters, bladder, and urethra. All 59 patients (100%) were found to have ipsilateral renal agenesis, and the diagnostic accuracy of ultrasound was 100%. The uterus was correctively diagnosed as complete bicorporal uterus in 42 cases (71.2%), bicorporal septate uterus in 7 cases (11.9%), complete uterus septate in 8 cases (13.6%), partial uterus septate in 1 case (1.7%), and unilateral isthmus atresia in 1 case (1.7%). The cervix was correctively diagnosed as septate cervix in 28 cases (47.5%), double cervix in 17 cases (28.8%), unilateral small cervix in 5 cases (8.5%), unilateral obliterated cervical orifice in 5 cases (8.5%), partial development of the unilateral cervix with a blind end in 3 cases (5.1%), and unilateral completely undeveloped cervix appearing as a normal cervix in 1 case (1.7%). The vagina was correctively diagnosed as oblique vaginal septum (OVS) in 45 cases (76.3%), and normal vagina in 13 cases (22.0%) via preoperative ultrasound. In 1 case (1/59, 1.7%) of high OVS with ipsilateral obliterated external cervical orifice, the OVS was missed by preoperative ultrasound. The ultrasound diagnostic accuracy rates of uterine malformation, cervical malformation, vaginal malformation, hematoma location and volume, uterine communication, and cervical communication were respectively 100%, 100%, 98.3%, 100%, 100%, and 100%. The ultrasonic detection rate for a hole on the OVS was 0%, and the missed diagnosis rate was 100%. SSUS can be used to accurately evaluate uterine, cervical, and vaginal malformation, obstruction site, location and volume of keratocele, cervical or uterine communication, and ovarian endometriosis cyst in patients with UGTOIRA syndrome and ipsilateral urinary system malformation. However, ultrasound is unable to identify a hole on the OVS.

The role of immune mechanisms in the pathogenesis of hemorrhagic fever with renal syndrome

Hemorrhagic fever with renal syndrome (HFRS) is an acute natural focal disease of a viral nature. Its severity is determined by hemorrhagic phenomena, cytokine storm, kidney damage with the development of acute renal failure, and the possibility of death. HFRS is caused by viruses from the family Hantaviridae. Hantaviruses are characterized by the ability to infect endothelial and epithelial cells of the renal tubules, as well as innate immunity cells (neutrophils, monocytes, dendritic cells), which leads to both direct damage to the immune system and indirect through a violation of their functions. The review analyzes the immune mechanisms in HFRS and their role in the pathogenesis of this disease.

In-cell Western assay to quantify infection with pathogenic orthohantavirus Puumala virus in replication kinetics and antiviral drug testing

Hemorrhagic fever with renal syndrome (HFRS) represents a serious zoonotic disease caused by orthohantaviruses in Eurasia. A specific antiviral therapy is not available. HFRS is characterized by acute kidney injury (AKI) with often massive proteinuria. Infection of kidney cells may contribute to the clinical picture. However, orthohantaviral replication in kidney cells is not well characterized. Therefore, we aimed to perform a reliable high-throughput assay that allows the quantification of infection rates and testing of antiviral compounds in different cell types. We quantified relative infection rates of Eurasian pathogenic Puumala virus (PUUV) by staining of nucleocapsid protein (N protein) in an in-cell Western (ICW) assay. Vero E6 cells, derived from the African green monkey and commonly used in viral cell culture studies, and the human podocyte cell line CIHP (conditionally immortalized human podocytes) were used to test the ICW assay for replication kinetics and antiviral drug testing. Quantification of infection by ICW revealed reliable results for both cell types, as shown by their correlation with immunofluorescence quantification results by counting infected cells. Evaluation of antiviral efficacy of ribavirin by ICW assay revealed differences in the toxicity (TC) and inhibitory concentrations (IC) between Vero E6 cells and podocytes. IC5O of ribavirin in podocytes is about 12-fold lower than in Vero E6 cells. In summary, ICW assay together with relevant human target cells represents an important tool for the study of hantaviral replication and drug testing.

A case of pulmonary tuberculosis patient complicated with hemorrhagic fever with renal syndrome and scrub typhus in Yunnan, China: a case report

BackgroundHemorrhagic fever with renal syndrome (HFRS) caused by Orthohantavirus (OHV) and scrub typhus (ST) caused by Orientia tsutsugamushi (OT) are two infectious diseases prevalent in southwest China. Rodents are the natural host and the main source of the two diseases. OT infection to humans is usually resulted from bite of an infective chigger mite on rodents, and OHV is transmitted through contact or inhalation of aerosols and secretions from infected rodent. The use of antibiotics and hormones is crucial for infectious diseases, although the clinical manifestations are not obvious and a definitive diagnosis becomes more difficult in the presence of these drugs. Clinically, fever is the first symptom of these two diseases, and most of them are accompanied by common symptoms such as chills and headaches. The clinical symptoms of these two diseases are very similar and therefore it is not easy to make a differential diagnosis.Case presentationIn this case, a 44-year-old male famer with pulmonary tuberculosis and a history of working in coal transportation was admitted to the hospital because of respiratory symptoms accompanied by fever, headache, and skin rashes on his body. Biochemical and urinalysis revealed the hepatic and renal injury. The subsequent molecular testing confirmed he suffered from HFRS and scrub typhus simultaneously that the serological and clinical diagnosis could not identify the cause of infection before. Such case has not been reported in Yunnan Province before.ConclusionThe clinical diagnosis should be combined with serological and nucleic acid testing approaches for differential diagnosis in areas where HFRS and ST are endemic.

The Role of Morphology in Predicting Fumarate Hydratase-deficient Uterine Leiomyomas in Young Women.

Hereditary leiomyomatosis and renal cell carcinoma is caused by germline mutations in the fumarate hydratase (FH) gene and is associated with an increased incidence of leiomyomas and a potentially aggressive variant of renal cell carcinoma. Pathologic evaluation of uterine leiomyoma can provide an opportunity for early recognition of the syndrome. We reviewed all archived slides of the cases to identify the characteristic morphologic features described for FH-deficient leiomyomas. We performed immunohistochemistry on whole sections of patients with uterine leiomyoma to evaluate for both FH and 2-succinocysteine (2SC) expression. Of the 106 cases, 19 showed the characteristic eosinophilic nucleoli with perinuclear halos, and 24 revealed a characteristic eosinophilic cytoplasmic inclusion consisting of pink globules present within the cytoplasm. Both of these morphologic findings were present together in 15 cases, and hemangiopericytomatous vessels were detected in 23 cases. The loss of FH protein expression was detected in 14 out of 106 cases (13%), and 13 out of 106 cases (12%) were positive for 2SC. We detected 10 cases with both 2SC-positive and FH expression loss. The presence of eosinophilic nucleoli with perinuclear halos and eosinophilic cytoplasmic inclusion was associated with both loss of FH protein expression and 2SC positivity ( P < 0.001). These findings underscore the importance of hematoxylin and eosin-based predictive morphology in FH-deficient uterine leiomyomas. Therefore, morphologic assessment of uterine leiomyomas for features of FH deficiency can serve as a screening tool for hereditary leiomyomatosis and renal cell carcinoma syndrome, allowing patients to be divided according to their hereditary risk assessment.

Study on the Effectiveness of Prevention Propaganda and Health Insurance Policies Dissemination of Hemorrhagic Fever with Renal Syndrome (HFRS) in Weinan City of Shaanxi Province

Weinan City is a high-prevalence area for Hemorrhagic Fever with Renal Syndrome (HFRS) in China, and the knowledge of HFRS prevention and relevant health insurance policies are related to the health and life of all residents. In order to study the effect of disease prevention propaganda and health insurance policies dissemination of HFRS in Weinan City, Shaanxi Province, this paper obtained survey samples by distributing and returning questionnaires, and the results of the questionnaire data were screened, organized and correlated, resulting in the results of the empirical study. That is, the effectiveness of HFRS prevention propaganda and health insurance policies dissemination in Weinan City was poor, and a significant positive correlation was found between respondents disease perception of HFRS and their knowledge of related health insurance policies, and this finding was interpreted using KAP and HBM theories. Discussions about strengthening IPC and leveraging Internet media to complete the transition from health beliefs to health behaviors are also presented.

Clinical and Molecular Epidemiology of Hemorrhagic Fever with Renal Syndrome Caused by Orthohantaviruses in Xiangyun County, Dali Prefecture, Yunnan Province, China.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease transmitted by several rodent species. We obtained clinical data of HFRS patients from the medical records of the People's Hospital of Xiangyun County in Dali Prefecture from July 2019 to August 2021. We collected epidemiological data of HFRS patients through interviews and investigated host animals using the night clip or night cage method. We systematically performed epidemiological analyses of patients and host animals. The differences in the presence of rodent activity at home (χ2 = 8.75, p = 0.031 < 0.05), of rodent-proof equipment in the food (χ2 = 9.19, p = 0.025 < 0.05), and of rodents or rodent excrement in the workplace (χ2 = 10.35, p = 0.014 < 0.05) were statistically different in the four clinical types, including mild, medium, severe, and critical HFRS-associated diseases. Furthermore, we conducted molecular detection of orthohantavirus in host animals. The total orthohantavirus infection rate of rodents was 2.72% (9/331); the specific infection rate of specific animal species was 6.10% (5/82) for the Apodemus chevrieri, 100% (1/1) for the Rattus nitidus, 3.77% (2/53) for the Rattus norvegicus, and 12.50% (1/8) for the Crocidura dracula. In this study, a total of 21 strains of orthohantavirus were detected in patients and rodents. The 12 orthohantavirus strains from patients showed a closer relationship with Seoul orthohantavirus (SEOOV) L0199, DLR2, and GZRn60 strains; the six orthohantavirus strains from Rattus norvegicus and Apodemus chevrieri were closely related to SEOOV GZRn60 strain. One strain (XYRn163) from Rattus norvegicus and one strain (XYR.nitidus97) from Rattus nitidus were closely related to SEOOV DLR2 strain; the orthohantavirus strain from Crocidura dracula was closely related to the Luxi orthohantavirus (LUXV) LX309 strain. In conclusion, patients with HFRS in Xuangyun County of Dali Prefecture are predominantly affected by SEOOV, with multiple genotypes of orthohantavirus in host animals, and, most importantly, these orthohantavirus strains constantly demonstrated zoonotic risk in humans.

Pathogenetic significance of CD3+CD56+ T-lymphocytes in hemorrhagic fever with renal syndrome

Aim to evaluate the pathogenetic role of T-lymphocytes carrying the natural killer marker CD56 in hemorrhagic fever with renal syndrome (HFRS).&#x0D; Material and methods. The study group included 65 patients with HFRS receiving the inpatient treatment in the Clinics of SamSMU, and 15 healthy people were chosen for the control group. The following examinations were scheduled for all patients in the different stages of the disease: a clinical blood test, flow cytometry with a given set of monoclonal antibodies, enzyme-linked immunosorbent assay of blood serum to determine the cytokine profile. For statistical analysis we used the SPSS v.23 software.&#x0D; Results. The percentage of CD3+ CD56+ NKT blood content in comparison with those for cells of innate immunity (neutrophil granulocytes, monocytes, natural killers) and lymphocytes of adaptive immune response, as well as the level of cytokines in the blood serum showed that in polyuric and convalescent periods, the number of these cells significantly increases and remains closely embedded in correlations with other components of the immune system.&#x0D; Conclusion. A new hypothesis has been proposed to interpret the role of NKT in the development of the immune response in HFRS.

Hereditary leiomyomatosis and renal cell cancer syndrome

Introduction: Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a rare autosomal dominantly inherited cancer predisposing syndrome giving rise to cutaneous and uterine leiomyomatosis, leiomyosarcoma and renal cell cancer. Patients with this syndrome harbours germline pathogenic variants in the fumarate hydratase (FH) gene.Case presentation: A 28-year-old Sri Lankan female, a product of a consanguineous marriage with strong family history of young onset fibroids presented with progressive dysmenorrhea, menorrhagia and irregular menstrual cycles for 2 years duration. There was recent onset lower abdominal colicky pain lasting for 3-5 min occurring during the post coital and intermenstrual period over 2 months. Examination did not reveal abnormal skin lesions or abdominal masses.Ultrasound examination revealed enlarged uterus with 2 large fibroids in the posterior wall and fundus of the uterus. She underwent laparoscopic myomectomy without perioperative complications. Histology revealed a leiomyoma with morphological features supporting the variant “fumarate hydratase deficient leiomyoma”.Whole exome sequencing of the patient revealed her to be harbouring a pathogenic variant c.878T&gt;G| p:Val293Gly in the FH gene for which she was heterozygous confirming that she had inherited the cancer predisposing syndrome of hereditary leiomyomatosis and renal cell cancer(HLRCC). Postoperatively her symptoms resolved, and she was able to sustain an uncomplicated pregnancy one year after. Currently she is closely followed up for future development of tumors including renal cell cancer bothclinically and via imaging.Conclusion: HLRCC is a rare autosomal dominantly inherited cancer syndrome predisposing to skin, uterine and renal tumors warranting surveillance at a younger age.

MOCOS-associated renal syndrome in a Brown Swiss cattle.

A recessive form of MOCOS-associated xanthinuria type II is described in Tyrolean grey cattle. A similar case was identified in a 5-month-old Brown Swiss calf with hoof overgrowth, rough coat, urine sediment, and pneumonia. To characterize the disease phenotype, to evaluate its genetic etiology, and to determine the prevalence of the deleterious allele in the Brown Swiss population. An affected calf, its parents, and 65 441 Swiss dairy cattle. The affected animal was clinically examined and necropsied. Microarray genotyping was used to determine the genotypes and to assess the frequency of the MOCOS allele in a Brown Swiss control cohort. Ultrasonography revealed hyperechoic renal pyramids with multifocal distal shadowing and echogenic sediment in the urinary bladder. Necropsy revealed suppurative bronchopneumonia and urolithiasis. Histology revealed numerous nephroliths with multifocal chronic lymphohistiocytic interstitial infiltrates, fibrosis, tubular degeneration, chronic multifocal glomerulonephritis with sclerosis, and bilateral hydronephrosis. Dysplastic changes were observed in the corium of the claw and the cornea. Genetic testing identified the homozygous presence of a known MOCOS frameshift variant in the case. Both parents were heterozygous and the prevalence of carriers in genotyped Brown Swiss cattle was 1.4% (342/24337). The findings were consistent with the diagnosis of a recessive renal syndrome similar to xanthinuria type II described in Tyrolean grey cattle. The prevalence of the deleterious MOCOS allele is low in the Brown Swiss breed. However, mating of carriers should be avoided to prevent further losses.

Опыт проведения контроля эффективности барьерной зимней дератизации на территории природного очага геморрагической лихорадки с почечным синдромом в Республике Башкортостан

The first experience of specialists of the Center for Hygiene and Epidemiology in the Republic of Bashkortostan to control the effectiveness of large-scale barrier winter deratization around settlements with high morbidity of hemorrhagic fever with renal syndrome (HFRS) is presented. For the first time in the territory of the Republic of Bashkortostan, barrier deratization was carried out in the winter period (February – March 2023) in order to improve the natural focus of HFRS on epidemic indications. Zoological, statistical, and epidemiological methods of research were used in the collection and analysis of data. According to zoological observations in the fall of 2022, the number of rodents in stationary points was 24.4 % per 100 trap-days, 2 times higher than in the fall of 2021. The peculiarity of weather conditions is high snow cover (up to 40 cm) and frost (up to minus 26 °C). The peculiarity of work: snowmobiles compacted snow in order to pass to the forest belt for spreading poisoned baits and setting traps. New data on the methodology of work – preliminary geocoding – determination of work sites (deratization and subsequent assessment of infestation after deratization) on the basis of mapping, according to the data of infection sites of patients with HFRS were presented. Features of the work are: participation of employees of different specialties (disinfectologists, biologists, zoologists, entomologist, assistants of medical epidemiologist), large-scale (4830 traps), compressed timing of work (February – March), 1030 days after winter deratization, interaction with the administration of the settlement. The technical complexity of setting traps to the level of "ground" in snow is described. Practical assistance of employees of research institutes, anti-plague institution, Reference centers for HFRS was noted. According to the results of external control of effectiveness after barrier deratization in winter, the number of small mammals in the farmsteads of settlements in 10–30 days after its completion did not exceed the normative index of 3 %, and in the forest belt around settlements did not exceed the normative index of 7 %. Keywords: small mammals, efficacy, trap-day, winter barrier deratization, hemorrhagic fever with renal syndrome, personal protective equipment.

Влияние гелиометеорологических факторов на эпидемический процесс геморрагической лихорадки с почечным синдромом и прогнозирование заболеваемости на территории лесостепного и степного ландшафтов

On the territory of the Orenburg region over a 25-year period, we studied the influence of 43 helio-meteorological factors on the cumulative incidence of hemorrhagic fever with renal syndrome (HFRS) in the population of the forest-steppe and steppe landscapes. It is shown that in of the forest-steppe landscape the priority helio-meteorological risk factors for the incidence of HFRS were: an increase in precipitation in March of the current year and in October of the previous year, as well as an increase in the Wolf number with a shift relative to the incidence to the left by 6 years. On the territory of the steppe landscape, the leading helio-meteorological risk factors for the epidemic process of HFRS were: a decrease in precipitation in June of the previous year, an increase in precipitation in February of the current year, and an increase in the Wolf number with a shift to the left relative to the incidence by 3 years. We have obtained regression equations for a short-term (for the current year) forecast of the intensity of the epidemic process of HFRS, taking into account helio-meteorological factors in the territory of the forest-steppe and steppe landscapes. These mathematical equations have been tested against actual morbidity rates. They can be recommended for practical use, as well as further improvement of the model. Keywords: hemorrhagic fever with renal syndrome, forest-steppe and steppe landscapes, prognosis, incidence.

A challenging case of microscopic polyangiitis with pulmonary–renal syndrome under the first wave of the COVID-19 epidemic

A challenging case of microscopic polyangiitis with pulmonary–renal syndrome under the first wave of the COVID-19 epidemic

Predictive value of CD4+CD8+ double positive T cells for the severity of hemorrhagic fever with renal syndrome

PurposesWe aimed to investigate the levels of CD4+CD8+ double positive (DP) T cells in patients with various severities of hemorrhagic fever with renal syndrome (HFRS), and the predictive capacity of DP T cells for the severity of this disorder. MethodsThe levels of DP T cells in 213 patients and 48 healthy donors were measured by flow cytometry, as were the levels of CD4+ T cells, CD8+ T cells, B lymphocytes, and natural killer (NK) cells. In each type of HFRS patient, we tested the basic clinical reference values for leukocytes, platelets, creatinine (Cr), uric acid (UA), and urea, and the values for activated partial thromboplastin time, prothrombin time, and fibrinogen, using conventional methods. The colloidal gold method was used to measure HFRS antibody levels in the patients. ResultsThe frequency of DP T cells increased with disease severity and peaked in patients with critical disease. Furthermore, the level of DP T cells proportionally correlated with the levels of Cr, UA, and urea in the serum. In contrast, there was an inverse correlation between DP T cells and platelets. Interestingly, the pattern of change in DP T cell frequency was similar to those of CD8+ T cells, B cells, and NK cells, but an inverse tendency was observed for CD4+ T cells. DP T cells demonstrated significant predictive value for the severity of HFRS. ConclusionsThe level of DP T cells is associated with HFRS severity, suggesting that it may be a potent indicator for the course of this disorder.

RIPK3 promotes hantaviral replication by restricting JAK-STAT signaling without triggering necroptosis

Hantaan virus (HTNV) is a rodent-borne virus that causes hemorrhagic fever with renal syndrome (HFRS), resulting in a high mortality rate of 15%. Interferons (IFNs) play a critical role in the anti-hantaviral immune response, and IFN pretreatment efficiently restricts HTNV infection by triggering the expression of a series of IFN-stimulated genes (ISGs) through the Janus kinase-signal transducer and activator of transcription 1 (JAK-STAT) pathway. However, the tremendous amount of IFNs produced during late infection could not restrain HTNV replication, and the mechanism remains unclear. Here, we demonstrated that receptor-interacting protein kinase 3 (RIPK3), a crucial molecule that mediates necroptosis, was activated by HTNV and contributed to hantavirus evasion of IFN responses by inhibiting STAT1 phosphorylation. RNA-seq analysis revealed the upregulation of multiple cell death-related genes after HTNV infection, with RIPK3 identified as a key modulator of viral replication. RIPK3 ablation significantly enhanced ISGs expression and restrained HTNV replication, without affecting the expression of pattern recognition receptors (PRRs) or the production of type I IFNs. Conversely, exogenously expressed RIPK3 compromised the host's antiviral response and facilitated HTNV replication. RIPK3−/− mice also maintained a robust ability to clear HTNV with enhanced innate immune responses. Mechanistically, we found that RIPK3 could bind STAT1 and inhibit STAT1 phosphorylation dependent on the protein kinase domain (PKD) of RIPK3 but not its kinase activity. Overall, these observations demonstrated a noncanonical function of RIPK3 during viral infection and have elucidated a novel host innate immunity evasion strategy utilized by HTNV.

Deep Sequencing to Reveal Phylo-Geographic Relationships of Juquitiba Virus in Paraguay.

Several hantaviruses result in zoonotic infections of significant public health concern, causing hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in the Old and New World, respectively. Given a 35% case fatality rate, disease-causing New World hantaviruses require a greater understanding of their biology, genetic diversity, and geographical distribution. Juquitiba hantaviruses have been identified in Oligoryzomys nigripes in Brazil, Paraguay, and Uruguay. Brazil has reported the most HCPS cases associated with this virus. We used a multiplexed, amplicon-based PCR strategy to screen and deep-sequence the virus harbored within lung tissues collected from Oligoryzomys species during rodent field collections in southern (Itapúa) and western (Boquerón) Paraguay. No Juquitiba-like hantaviruses were identified in Boquerón. Herein, we report the full-length S and M segments of the Juquitiba hantaviruses identified in Paraguay from O. nigripes. We also report the phylogenetic relationships of the Juquitiba hantaviruses in rodents collected from Itapúa with those previously collected in Canindeyú. We showed, using the TN93 nucleotide substitution model, the coalescent (constant-size) population tree model, and Bayesian inference implemented in the Bayesian evolutionary analysis by sampling trees (BEAST) framework, that the Juquitiba virus lineage in Itapúa is distinct from that in Canindeyú. Our spatiotemporal analysis showed significantly different time to the most recent ancestor (TMRA) estimates between the M and S segments, but a common geographic origin. Our estimates suggest the additional geographic diversity of the Juquitiba virus within the Interior Atlantic Forest and highlight the need for more extensive sampling across this biome.

Epizootic and epidemiological situation of hemorrhagic ever with renal syndrome in the Rostov region (2020–2022)

Objective: evaluation of the epizootic and epidemiological situation for HFRS in the Rostov region. Materials and methods: from 2020 to 2022, an enzyme-linked immunosorbent assay was used to study the presence of hantavirus antigens in samples of small mammals and class G immunoglobulins in the blood sera of healthy donors. Results: epizootological monitoring conducted in 35 administrative districts of the region and in the vicinity of Rostov-on-Don (2157 animals, 15 species) revealed the circulation of hantaviruses in populations of small mammals. Infection with hantaviruses of six species of mammals was registered: house mouse, common vole, yellow-bellied mouse, European forest mouse, East European vole, small forest mouse. 1062 blood samples from residents of various regions of the region were tested. Class G antibodies to hantaviruses were detected in 7.0%, 4.5%, 7.1% in different years. Conclusions: the coincidence in the territories of Azovsky, Kamensky, Neklinovsky, Salsky, Morozovsky districts of positive findings of the hantavirus antigen in samples of small mammals and seropositive samples of donors suggests the presence of a natural focus of HFRS, the establishment of boundaries and activity of which needs further research.