Hantavirus Antibodies Research Articles

Cross-reactivity of hantavirus antibodies after immunization with PUUV antigens.

Nephropathia epidemica (NE), caused by Puumala (PUUV) orthohantavirus, is endemic in the Republic of Tatarstan (RT). There are limited options for NE prevention in RT. Currently, available vaccines are made using Haantan (HNTV) orthohantavirus antigens. In this study, the efficacy of microvesicles (MVs) loaded with PUUV antigens to induce the humoral immune response in small mammals was analyzed. Additionally, the cross-reactivity of serum from immunized small mammals and NE patients with HNTV, Dobrava, and Andes orthohantaviruses was investigated using nucleocapsid (N) protein peptide libraries. Finally, the selected peptides were analyzed for allergenicity, their ability to induce an autoimmune response, and their interaction with Class II HLA. Several N protein peptides were found to be cross-reactive with serum from MVs immunized small mammals. These cross-reactive epitopes were located in oligomerization perinuclear targeting and Daxx-interacting domains. Most cross-reactive peptides lack allergenic and autoimmune reactivity. Molecular docking revealed two cross-reacting peptides, N6 and N19, to have good binding with three Class II HLA alleles. These peptides could be candidates for developing vaccines and therapeutics for NE.

Seroprevalence of Hantavirus among Manual Cane Cutters and Epidemiological Aspects of HPS in Central Brazil.

Hantavirus pulmonary syndrome (HPS) is a rodent-borne zoonotic disease that is endemic throughout the Americas. Agricultural activities increase exposure to wild rodents, especially for sugarcane cutters. We carried out a survey of the epidemiological aspects of HPS and investigated the prevalence of hantavirus infection in the sugarcane cutter population from different localities in the Brazilian Midwest region. We conducted a retrospective study of all confirmed HPS cases in the state of Goiás reported to the National HPS surveillance system between 2007 and 2017, along with a seroepidemiological study in a population of sugarcane cutters working in Goiás state in 2016, using the anti-hantavirus (Andes) ELISA IgG. A total of 634 serum samples from cane cutters were tested for hantavirus antibodies, with 44 (6.9%) being IgG-reactive according to ELISA. The destination of garbage was the only statistically significant variable (p = 0.03) related to the detection of hantavirus IgG (p < 0.05). We described the epidemiological profile of reported hantavirus cases in Goiás-a highly endemic area for HPS, and where the seroepidemiological study was conducted. Our results increase our knowledge about hantavirus infections in Brazil and highlight the vulnerability of sugarcane cutters to a highly lethal disease that, to date, has no specific treatment or vaccination.

Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies.

Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are relatively rare, mortality rates range from 1 to 40% depending on the hantavirus species. There are currently no FDA-approved vaccines or therapeutics for hantaviruses, and the only treatment for infection is supportive care for respiratory or kidney failure. Additionally, the human humoral immune response to hantavirus infection is incompletely understood, especially the location of major antigenic sites on the viral glycoproteins and conserved neutralizing epitopes. Here, we report antigenic mapping and functional characterization for four neutralizing hantavirus antibodies. The broadly neutralizing antibody SNV-53 targets an interface between Gn/Gc, neutralizes through fusion inhibition and cross-protects against the Old World hantavirus species Hantaan virus when administered pre- or post-exposure. Another broad antibody, SNV-24, also neutralizes through fusion inhibition but targets domain I of Gc and demonstrates weak neutralizing activity to authentic hantaviruses. ANDV-specific, neutralizing antibodies (ANDV-5 and ANDV-34) neutralize through attachment blocking and protect against hantavirus cardiopulmonary syndrome (HCPS) in animals but target two different antigenic faces on the head domain of Gn. Determining the antigenic sites for neutralizing antibodies will contribute to further therapeutic development for hantavirus-related diseases and inform the design of new broadly protective hantavirus vaccines.

Role of Seaports and Imported Rats in Seoul Hantavirus Circulation, Africa.

Seoul orthohantavirus (SEOV) is not considered a major public health threat on the continent of Africa. However, Africa is exposed to rodentborne SEOV introduction events through maritime traffic after exponential growth of trade with the rest of the world. Serologic studies have already detected hantavirus antibodies in human populations, and recent investigations have confirmed circulation of hantavirus, including SEOV, in rat populations. Thus, SEOV is a possible emerging zoonotic risk in Africa. Moreover, the range of SEOV could rapidly expand, and transmission to humans could increase because of host switching from the usual brown rat (Rattus norvegicus) species, which is currently invading Africa, to the more widely installed black rat (R. rattus) species. Because of rapid economic development, environmental and climatic changes, and increased international trade, strengthened surveillance is urgently needed to prevent SEOV dissemination among humans in Africa.

Urine excreted antibodies significance in the hemorrhagic fever with renal syndrome specific diagnosis

Relevance. Hemorrhagic fever with renal syndrome (HFRS) is an acute viral zoonosis. Being widespread in Eurasia, it holds a leading place in Russia among natural focal human diseases. The vast majority of HFRS cases in Russia, about 98%, are associated with Puumala virus. The disease is characterized by a wide range of clinical manifestations. Early specific diagnostics appears to be of a great importance for starting timely pathogenic therapy. The aim of the study was to clarify the diagnostic value of detecting hantavirus antibodies in the HFRS suspected patient urine. Materials and methods. Blood sera and urine samples from 68 patients at the Infectious Diseases Hospital in the city of Ufa, obtained with a 2-day interval, as well as urine and blood serum samples from 15 convalescents 1, 2, 3 and 6 months after disease onset were examined for hantavirus antibodies. 53 blood sera and urine samples from patients residing in Moscow, Moscow and Samara regions collected at different time points during the disease course were investigated in parallel. Antibodies were detected by the indirect immunofluorescence method. Results. On day 3, 4, 5 and 6 of disease, while specific antibodies were detected in the blood serum, antibodies in the urine were found in 85.7%, 89.4%, 93.1% and 100% of patients, respectively. The peak quantity of antibodies was excreted in the urine from days 5 to 11, which corresponds to the oliguric stage of the disease. In the convalescent period, antibodies were still detected in urine 1, 2 and 3 months afterwards in 86.7%, 46% and 20% of cases, respectively, but not detected 6 months later, which probably reflects the process of long-term restoration of the kidneys function. A moderate positive correlation between specific antibodies in serum and urine was observed only in the oliguric period of the disease. Conclusions. Detection of hantavirus antibodies simultaneously in blood serum and urine of febrile patients instead of paired blood sera allows to conduct HFRS diagnostics within the very first days of hospitalization and prevent severe complications due to timely pathogenic therapy.

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.

Distinct Genotype of Hantavirus Infection in Rodents in Jiangxi Province, China, in 2020–2021

Background: Hantavirus causes hemorrhagic fever with renal syndrome, thus posing a major threat to human health in Jiangxi Province, China. Both Hantaan virus (HTNV) and Seoul virus (SEOV) have been found to be endemic in the province. Methods: Rodents were trapped from Gaoan Anyi and Tonggu counties in Jiangxi Province in 2020–2021. Hantavirus specific antibodies in the blood and RNA in the lung samples from the captured mammals were detected and analyzed. Results: A total of 889 small mammals from seven species were collected. Positive detection was observed for hantavirus antibodies in 9.8% (87/889), SEOV RNA in 1% (9/889) and HTNV RNA in 2.6% (23/889). The difference in detection rates between regions was significant. Phylogenetic analysis of the obtained partial sequences of M and S segments revealed that two distinct genotypes of HTNV and three genotypes of SEOV were co-circulating in the captured mammals, with a regionally specific distribution. Conclusion: Multiple distinct genotypes of hantavirus are co-circulating in the province. Further studies in broader areas remain needed to reveal the diversity of hantaviruses.

Surveillance for hemorrhagic fever with renal syndrome in Zhejiang, 2016–2020

Objective To understand the epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS), the distribution, density and virus carriage of host animals in Zhejiang province, and provide scientific basis for the formulation of prevention and control measures. Methods The incidence data of HFRS in Zhejiang from 2016 to 2020 were collected for a descriptive epidemiological analysis to understand its time, place and population distributions. The host animals were investigated at 5 surveillance areas in Zhejiang, the capture rate was investigated by the night method, and rat-shaped animal lungs and blood were collected for the hantavirus antigen and antibody detections, and analysis on the distribution and virus carriage of rodents in Zhejiang were conducted. Results The annual reported case numbers and incidence rate of HFRS in Zhejiang were 349 and 0.62/100 000 in 2016, 353 and 0.63/100 000 in 2017, 327 and 0.59/100 000 in 2018, 369 and 0.63/100 000 in 2019, and 260 and 0.46/100 000 in 2020. From 2016 to 2020, a total of 14 068 rat traps were deployed in residential areas, and 622 rodents were captured, the capture rate was 4.42%, and a total of 31 875 rat traps were deployed in the field, and 2 112 rodents were captured, the capture rate was 6.63% in the 5 surveillance areas. The differences in rodent density in the filed among the 5 surveillance areas were significant (F=2.941, P=0.046). A total of 3 065 rodents were captured in the 5 surveillance areas. The predominant rodent species in the field was Apodemus agrarianus, (1 830, 59.71%); the predominant rodent species in residential areas was Rattus norvegicus (330, 10.77%), the difference was significant (χ2=1675.401, P＜0.001). A total of 3065 rodent serum samples were tested, and the antibody positive rate was 8.7% (236/2808), and a total of 3065 rodent lung specimens were tested, the antibody positive rate was 3.66% (103/2815), and the differences in rodent species which were antibody positive among the 5 surveillance areas were significant (χ2=235.762, P＜0.001); and the differences in rodent species which were antigen positive among the 5 surveillance areas were significant (χ2=116.195, P＜0.001). Conclusion The density and virus carrying rate of rodents were high in the areas with high incidence of HFRS in Zhejiang. It is necessary to take targeted prevention and control measures in key areas for the better prevention and control of HFRS.

Seroprevalence of three emerging arboviral infections in Kuwaiti nationals

Diseases caused by dengue, sandfly fever and hanta viruses pose a major health risk in many countries. We determined the threat of these arboviral infections through a serologic using enzyme linked immunosorbent assay (ELISA) based tests. Hantavirus-specific antibodies were also detected using immunofluorescence. Of 499 samples tested for dengue virus IgG antibodies l4% were as positive for dengue positive by all the ELISA tests. Among the 42 showing strong IgG reactivity, only 1 was positive for dengue virus IgM antibodies. All samples tested for IgG antibodies to sandfly fever virus were negative. Hantavirus antibodies were detected in 11% of the 46 samples from high-risk individuals. The low prevalences suggest that at present these infections are not a serious problem in Kuwait.

Prevalence and risk factors of Hantavirus infection in patients undergoing hemodialysis in Khartoum, Sudan, in 2019: a cross-sectional study.

Hantaviruses are enveloped negative sense RNA viruses that cause hemorrhagic fever with renal syndrome. This study aimed to identify the prevalence of Hantavirus IgG antibodies and possible risk factors for Hantaviruses infections among end-stage renal disease (ESRD) patients attending the Dr Salma dialysis center in Sudan. This was a cross-sectional study in which 91 ESRD patients and 30 healthy plasma samples were screened for Hantavirus IgG antibodies using ELISA. A questionnaire containing sociodemographics, history of rat exposure and clinical data information was filled in by each ESRD patient. In this study, 9 out of 91 ESRD patients (9.9%) tested positive for Hantaviruses antibodies (IgG) while none of the 30 healthy plasma samples showed seropositivity. There was no statistically significant association between age, gender, educational level and rat exposure and Hantavirus infection in ESRD patients (p>0.05). This study is the first to be conducted in Sudan regarding Hantaviruses and ESRD. The prevalence of Hantavirus antibodies among ESRD patients is high compared with findings reported in the literature from studies conducted on the same group of patients. It points to an interesting question as to whether Hantaviruses have an association with ESRD but further studies are needed before drawing any conclusions.

Hantavirus antibodies among phyllostomid bats from the arc of deforestation in Southern Amazonia, Brazil.

In order to determine whether southern Amazonian bats could harbour hantaviruses we, serologically and molecularly, screened blood, saliva, excreta and organ tissues of 47 bats captured from September to December 2015. We found that only phyllostomid bats presented antibodies against hantavirus. The seropositive bats belonged to two species of Phyllostomid bats: the greater spear-nosed bat Phyllostomus hastatus (omnivorous) and the gnome fruit-eating bat Dermanura gnoma. The overall seroprevalence was of 4.2%. Therefore, we show here that hantaviruses are circulating among phyllostomid bats in the Amazonian arc of deforestation.

Mechanisms of Hantavirus Transmission in Oligoryzomys longicaudatus.

The cricetid rodent Oligoryzomys longicaudatus is the species host of Andes virus (ANDV) which causes hantavirus pulmonary syndrome in southern Argentina and Chile. Population density, behavioral interactions, and spacing patterns are factors that affect viral transmission among wild rodents. We predict that the highest prevalence of hantavirus antibody positive would be found among wounded, reproductive males and that, at high population densities, wounded, reproductive males would be dispersers rather than resident individuals. The study was conducted seasonally from October (spring) 2011 to October (spring) 2013 in a shrubland habitat of Cholila, Argentina. During each trapping session, we classified captured O. longicaudatus as resident or disperser individuals, estimated population density, and recorded wounds as an indicator of aggression among individuals. We obtained blood samples from each individual for serological testing. We used generalized linear models to test the statistical significance of association between antibody prevalence, and sex, resident/dispersal status, wounds and trapping session. The highest proportion of seropositive O. longicaudatus individuals was among wounded reproductive males during periods of the greatest population density, and the characteristics of seroconverted individuals support that transmission is horizontal through male intrasexual competition. A positive association between dispersing individuals and hantavirus antibody was detected at high population density. Our study design allowed us to obtain data on a large number of individuals that are seroconverted, enabling a better understanding of the ecology and epidemiology of the ANDV host system.

Detection of New World Hantavirus Antibodies in Rodents of Eastern New Mexico, USA

Hantaviruses, causal agents of the potentially lethal hantavirus pulmonary syndrome, have widely distributed rodent hosts. Using an enzyme-linked immunosorbent assay, we tested blood from 398 wild rodents captured in eastern New Mexico, US in 2015-17 and found 42 antibody-positive samples representing six genera.

Molecular detection of viruses causing hemorrhagic fevers in rodents in the south-west of Korea.

Many pathogens causing hemorrhagic fevers of medical and veterinary importance have been identified and isolated from rodents in the Republic of Korea (ROK). We investigated the occurrence of emerging viruses causing hemorrhagic fevers, such as hemorrhagic fever with renal syndrome (HFRS), severe fever with thrombocytopenia syndrome (SFTS), and flaviviruses, from wild rodents. Striped field mice, Apodemus agrarius (n = 39), were captured during 2014-2015 in the south-west of ROK. Using molecular methods, lung samples were evaluated for SFTS virus, hantavirus, and flavivirus, and seropositivity was evaluated in the blood. A high positive rate of hantavirus (46.2%) was detected in A. agrarius lungs by reverse transcription-nested polymerase chain reaction (RT-N-PCR). The monthly occurrence of hantavirus was 16.7% in October, 86.7% in November, and 25% in August of the following year (p < 0.001). Moreover, 17.9% of blood samples were serologically positive for hantavirus antibodies. The most prevalent strain in A. agrarius was Hantaan virus. All samples were positive for neither SFTS virus nor flavivirus. Hantaan virus was detected in 86.7% of A. agrarius in November (autumn), and thus, virus shedding from A. agrarius can increase the risk of humans contracting HFRS. These findings may help to predict and prevent disease outbreaks in ROK.

Rodent Abundance and Hantavirus Infection in Protected Area, East-Central Argentina.

We captured 3 hantavirus rodent hosts in Otamendi Natural Reserve, Argentina, during 2007–2012. Hantavirus antibodies were found only in Akodon azarae grass mice, mainly in males and old animals. Higher abundance of this species was associated with warm and rainy weather and high water levels, which peaked after a strong El Niño event.

Species Identity Supersedes the Dilution Effect Concerning Hantavirus Prevalence at Sites across Texas and México.

Recent models suggest a relationship exists between community diversity and pathogen prevalence, the proportion of individuals in a population that are infected by a pathogen, with most inferences tied to assemblage structure. Two contrasting outcomes of this relationship have been proposed: the "dilution effect" and the "amplification effect." Small mammal assemblage structure in disturbed habitats often differs from assemblages in sylvan environments, and hantavirus prevalence is often negatively correlated with habitats containing high species diversity via dilution effect dynamics. As species richness increases, prevalence of infection often is decreased. However, anthropogenic changes to sylvan landscapes have been shown to decrease species richness and/or increase phylogenetic similarities within assemblages. Between January 2011 and January 2016, we captured and tested 2406 individual small mammals for hantavirus antibodies at 20 sites across Texas and México and compared differences in hantavirus seroprevalence, species composition, and assemblage structure between sylvan and disturbed habitats. We found 313 small mammals positive for antibodies against hantaviruses, evincing an overall prevalence of 9.7% across all sites. In total, 40 species of small mammals were identified comprising 2 taxonomic orders (Rodentia and Eulipotyphla). By sampling both habitat types concurrently, we were able to make real-world inferences into the efficacy of dilution effect theory in terms of hantavirus ecology. Our hypothesis predicting greater species richness higher in sylvan habitats compared to disturbed areas was not supported, suggesting the characteristics of assemblage structure do not adhere to current conceptions of species richness negatively influencing prevalence via a dilution effect.

INTERSPECIFIC COMPARISON OF HANTAVIRUS PREVALENCE IN PEROMYSCUS POPULATIONS FROM A FRAGMENTED AGRO-ECOSYSTEM IN INDIANA, USA.

Comparatively little is known about hantavirus prevalence within rodent populations from the Midwestern US, where two species of native mice, the prairie deer mouse ( Peromyscus maniculatus bairdii) and the white-footed mouse ( Peromyscus leucopus noveboracensis), are dominant members of rodent communities. We sampled both species in central Indiana and tested individuals for presence of hantavirus antibodies to determine whether seroprevalence (percent of individuals with antibodies reactive to Sin Nombre virus antigen) differed between species, or among different habitat types within fragmented agro-ecosystems. Prevalence of hantavirus antibodies varied significantly between species, with seroprevalence in prairie deer mice (21.0%) being nearly four times higher than in white-footed mice (5.5%). Seroprevalence was almost eight times higher within the interior of row-crop fields (37.7%) occupied solely by prairie deer mouse populations, relative to field edges (5.2%) or adjacent forest habitat (6.1%). In the fragmented Midwestern agro-ecosystem of this study, prairie deer mice appear to be the dominant hantavirus reservoir, with particularly high seroprevalence in populations within the interior of row-crop fields.

Prediction of Pan-Specific B-Cell Epitopes From Nucleocapsid Protein of Hantaviruses Causing Hantavirus Cardiopulmonary Syndrome.

Hantaviruses are emerging viral pathogens that causes hantavirus cardiopulmonary syndrome (HCPS) in the Americas, a severe, sometimes fatal, respiratory disease in humans with a case fatality rate of ≥50%. IgM and IgG-based serological detection methods are the most common approaches used for laboratory diagnosis of hantaviruses. Such emerging viral pathogens emphasizes the need for improved rapid diagnostic devices and vaccines incorporating pan-specific epitopes of genotypes. We predicted linear B-cell epitopes for hantaviruses that are specific to genotypes causing HCPS in humans using in silico prediction servers. We modeled the Andes and Sin Nombre hantavirus nucleocapsid protein to locate the identified epitopes. Based on the mean percent prediction probability score, epitope IMASKSVGS/TAEEKLKKKSAF was identified as the best candidate B-cell epitope specific for hantaviruses causing HCPS. Promiscuous epitopes were identified in the C-terminal of the protein. Our study for the first time has reported pan-specific B-cell epitopes for developing immunoassays in the detection of antibodies to hantaviruses causing HCPS. Identification of epitopes with pan-specific recognition of all genotypes causing HCPS could be valuable for the development of immunodiagnositic tools toward pan-detection of hantavirus antibodies in ELISA. J. Cell. Biochem. 118: 2320-2324, 2017. © 2017 Wiley Periodicals, Inc.

High Prevalence of Tula Hantavirus in Common Voles in The Netherlands.

Tula virus (TULV) is a zoonotic hantavirus. Knowledge about TULV in the Netherlands is very scarce. Therefore in 2014, 49 common voles (Microtus arvalis) from a region in the south of the Netherlands, and in 2015, 241 common voles from regions in the north of the Netherlands were tested with the TULV quantitative RT-PCR. In the southern region, prevalence of TULV was 41% (20/49). In the northern regions, prevalence ranged from 12% (4/34) to 45% (17/38). Phylogenetic analysis of the obtained sequences showed that the regions fall within different clusters. Voles from the south were also tested on-site for the presence of hantavirus antibodies, but serology results were poorly associated with qRT-PCR results. These findings suggest that TULV may be more widespread than previously thought. No human TULV cases have been reported thus far in the Netherlands, but differentiation between infection by TULV or the closely related Puumala virus is not made in humans in the Netherlands, thus cases may be misdiagnosed.

How much effort is required to accurately describe the complex ecology of a rodent-borne viral disease?

We use data collected on 18,1-ha live trapping grids monitored from 1994 through 2005 and on five of those grids through 2013 in the mesic northwestern US to illustrate the complexity of the deer mouse (Peromyscus maniculatus)/Sin Nombre virus (SNV) host-pathogen system. Important factors necessary to understand zoonotic disease ecology include those associated with distribution and population dynamics of reservoir species as well as infection dynamics. Results are based on more than 851,000 trap nights, 16,608 individual deer mice and 10,572 collected blood samples. Deer mice were distributed throughout every habitat we sampled and were present during every sampling period in all habitats except high altitude habitats over1900 m. Abundance varied greatly among locations with peak numbers occurring mostly during fall. However, peak rodent abundance occurred during fall, winter and spring during various years on three grids trapped 12 mo/yr. Prevalence of antibodies to SNV averaged 3.9% to 22.1% but no grids had mice with antibodies during every month. The maximum period without antibody-positive mice ranged from one month to 52 months, or even more at high altitude grids where deer mice were not always present. Months without antibody-positive mice were more prevalent during fall than spring. Population fluctuations were not synchronous over broad geographic areas and antibody prevalences were not well spatially consistent, differing greatly over short distances. We observed an apparently negative, but non-statistically significant relationship between average antibody prevalence and average deer mouse population abundance and a statistically significant positive relationship between the average number of antibody positive mice and average population abundance. We present data from which potential researchers can estimate the effort required to adequately describe the ecology of a rodent-borne viral system. We address different factors affecting population dynamics and hantavirus antibody prevalence and discuss the path to understanding a complex rodent-borne disease system as well as the obstacles in that path.