Hantavirus Pulmonary Syndrome Research Articles

Assessing Pulmonary Epithelial Damage in Hantavirus Cardiopulmonary Syndrome: Challenging the Predominant Role of Vascular Endothelium through sRAGE as a Potential Biomarker.

Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory illness primarily associated with microvascular endothelial changes, particularly in the lungs. However, the role of the pulmonary epithelium in HCPS pathogenesis remains unclear. This study explores the potential of soluble Receptors for Advanced Glycation End-products (sRAGE) as a biomarker for assessing pulmonary epithelial damage in severe HCPS, challenging the prevailing view that endothelial dysfunction is the sole driver of this syndrome. We conducted a cross-sectional study on critically ill HCPS patients, categorizing them into mild HCPS, severe HCPS, and negative control groups. Plasma sRAGE levels were measured, revealing significant differences between the severe HCPS group and controls. Our findings suggest that sRAGE holds promise as an indicator of pulmonary epithelial injury in HCPS and may aid in tracking disease progression and guiding therapeutic strategies. This study brings clarity on the importance of investigating the pulmonary epithelium's role in HCPS pathogenesis, offering potential avenues for enhanced diagnostic precision and support in this critical public health concern.

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.

Zoonotic Hantaviridae with Global Public Health Significance.

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.

Two point mutations in protocadherin-1 disrupt hantavirus recognition and afford protection against lethal infection

Andes virus (ANDV) and Sin Nombre virus (SNV) are the etiologic agents of severe hantavirus cardiopulmonary syndrome (HCPS) in the Americas for which no FDA-approved countermeasures are available. Protocadherin-1 (PCDH1), a cadherin-superfamily protein recently identified as a critical host factor for ANDV and SNV, represents a new antiviral target; however, its precise role remains to be elucidated. Here, we use computational and experimental approaches to delineate the binding surface of the hantavirus glycoprotein complex on PCDH1’s first extracellular cadherin repeat domain. Strikingly, a single amino acid residue in this PCDH1 surface influences the host species-specificity of SNV glycoprotein-PCDH1 interaction and cell entry. Mutation of this and a neighboring residue substantially protects Syrian hamsters from pulmonary disease and death caused by ANDV. We conclude that PCDH1 is a bona fide entry receptor for ANDV and SNV whose direct interaction with hantavirus glycoproteins could be targeted to develop new interventions against HCPS.

Hantavirus Infections among Military Forces.

Hantaviruses cause two kinds of clinical syndromes. Hemorrhagic fever with renal syndrome is caused by Hantaan virus in Asia, Puumala virus (PUUV) and Dobrava virus in Europe, and Seoul virus worldwide. Hantavirus cardiopulmonary syndrome is caused by Sin Nombre virus in North America and Andes virus and related viruses in Latin America. All hantaviruses are carried by rodents and insectivores. Humans are infected via inhaled aerosols of rodent excreta. In the history, there are several epidemics of acute infectious diseases during many wars, which have been suggested or proven to be caused by various hantaviruses. Literature review of 41 original publications and reviews published between 1943 and 2022 was performed. Among them, 23 publications handle hantavirus infections among military forces, and the rest 17 hantavirus infections themselves. A large epidemic during World War II in 1942 among German and Finnish soldiers in Northern Finland with more than 1,000 patients was most probably caused by PUUV. During Korean War in 1951-1954,∼ 3,200 cases occurred among United Nations soldiers in an epidemic caused by Hantaan virus. During Balkan war from 1991 to 1995, numerous soldiers got ill because of hantavirus infection caused by PUUV and Dobrava virus. Several other reports of cases of various hantavirus infections especially among U.S. soldiers acting in South Korea, Germany, Bosnia, and Kosovo have been described in the literature. Military maneuvers usually include soil removal, spreading, digging with accompanied dust, and living in field and other harsh conditions, which easily expose soldiers to rodents and their excreta. Therefore, the risks of hantavirus infections in military context are obvious. All military infections have been caused by hantaviruses leading to hemorrhagic fever with renal syndrome.

Hantavirus in Panama: Twenty Years of Epidemiological Surveillance Experience.

Twenty years have passed since the emergence of hantavirus zoonosis in Panama at the beginning of this millennium. We provide an overview of epidemiological surveillance of hantavirus disease (hantavirus pulmonary syndrome and hantavirus fever) during the period 1999-2019 by including all reported and confirmed cases according to the case definition established by the health authority. Our findings reveal that hantavirus disease is a low-frequency disease, affecting primarily young people, with a relatively low case-fatality rate compared to other hantaviruses in the Americas (e.g., ANDV and SNV). It presents an annual variation with peaks every 4-5 years and an interannual variation influenced by agricultural activities. Hantavirus disease is endemic in about 27% of Panama, which corresponds to agroecological conditions that favor the population dynamics of the rodent host, Oligoryzomys costaricensis and the virus (Choclo orthohantavirus) responsible for hantavirus disease. However, this does not rule out the existence of other endemic areas to be characterized. Undoubtedly, decentralization of the laboratory test and dissemination of evidence-based surveillance guidelines and regulations have standardized and improved diagnosis, notification at the level of the primary care system, and management in intensive care units nationwide.

Two Decades of Wildlife Pathogen Surveillance: Case Study of Choclo orthohantavirus and Its Wild Reservoir Oligoryzomys costaricensis.

The Costa Rican pygmy rice rat (Oligoryzomys costaricensis) is the primary reservoir of Choclo orthohantavirus (CHOV), the causal agent of hantavirus disease, pulmonary syndrome, and fever in humans in Panama. Since the emergence of CHOV in early 2000, we have systematically sampled and archived rodents from >150 sites across Panama to establish a baseline understanding of the host and virus, producing a permanent archive of holistic specimens that we are now probing in greater detail. We summarize these collections and explore preliminary habitat/virus associations to guide future wildlife surveillance and public health efforts related to CHOV and other zoonotic pathogens. Host sequences of the mitochondrial cytochrome b gene form a single monophyletic clade in Panama, despite wide distribution across Panama. Seropositive samples were concentrated in the central region of western Panama, consistent with the ecology of this agricultural commensal and the higher incidence of CHOV in humans in that region. Hantavirus seroprevalence in the pygmy rice rat was >15% overall, with the highest prevalence in agricultural areas (21%) and the lowest prevalence in shrublands (11%). Host-pathogen distribution, transmission dynamics, genomic evolution, and habitat affinities can be derived from the preserved samples, which include frozen tissues, and now provide a foundation for expanded investigations of orthohantaviruses in Panama.

Incidence of Orthohantavirus infection in humans follows observed changes in rodent reservoirs, Hubei Province, China (1984-2010).

Orthohantaviruses (genus Orthohantavirus, family Hantaviridae of order Bunyavirales) are rodent-borne viruses causing 2 human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), which are mainly prevalent in Eurasia and the Americas, respectively. We initiated this study to investigate and analyze the Orthohantaviruses infection in rodent reservoirs and humans in the Hubei Province of China from 1984 to 2010. The study included 10,314 mouse and 43,753 human serum samples. In this study, we analyzed the incidence of Orthohantavirus infection in humans and observed changes in rodent reservoirs in Hubei Province. The results indicated that although the incidence of HFRS declined from the 1990s, the human inapparent infection did not decrease dramatically. Although elements of the disease ecology have changed over the study period, Apodemus agrarius and Rattus norvegicus remain the major species and a constituent ratio of Rattus norvegicus increased. Rodent population density fluctuated between 16.65% and 2.14%, and decreased quinquennially, showing an obvious downward trend in recent years. The average orthohantaviruses-carrying rate was 6.36%, of which the lowest rate was 2.92% from 2006 to 2010. The analysis of rodent species composition showed that Rattus norvegicus and Apodemus agrarius were the dominant species over time (68.6% [1984 to 1987] and 90.4% [2000 to 2011]), while the composition and variety of other species decreased. The density of rodents was closely related to the incidence of HFRS (r = 0.910, P = .032). Our long-term investigation demonstrated that the occurrence of HFRS is closely related to rodent demographic patterns. Therefore, rodent monitoring and rodent control measures for prevention against HFRS in Hubei are warranted.

Hantavirus Diseases – A Comprehensive Review

Hantaviruses are a diverse group of infectious agents which are zoonotic in nature and transmitted to humans through rodent reservoir. Hantaviruses are enveloped RNA viruses that persistently infect rodent hosts without ill-effect. The host persistently excretes virus in urine and saliva. Man becomes infected from the rodents when one enters the ecological niche of the other. Hantaviruses can cause two types of diseases in humans: hemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS). The number of reported Hantavirus infections is increasing worldwide, and new Hantaviruses are being discovered in many countries, making them a global public health concern. Hantavirus infections are thought to be under diagnosed due to the fact that they frequently cause asymptomatic and nonspecific mild infections, as well as a lack of simple standardized diagnostic laboratory methods. This review summarizes current knowledge on Hantaviral infections, including virology, epidemiology, clinical manifestations, laboratory diagnostics, treatment, and prevention.

Design and validation of a novel multi-epitopes vaccine against hantavirus

Hantavirus is a member of the order Bunyavirales and an emerging global pathogen. Hantavirus infections have affected millions of people globally based on available epidemiological data and research studies. Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are the two main human diseases associated with hantavirus infections. Hence, efforts are required to develop a potent vaccine against the pathogen. The only vaccine that is in use for hantavirus is an inactivated virus vaccine, “Hantavax”, but it failed to produce neutralizing antibodies. Vaccine development is of much importance in dealing with the surge of hantavirus globally. In this study, hantavirus five proteins (N protein, G1 and G2, L protein, and non-structural proteins) were used in NetCTL 1.2 program to predict T-cell epitopes. To predict major histocompatibility complex (MHC) binding alleles, an immune epitope database (IEDB) was used. All predicted epitopes were then investigated for different immunoinformatics analyses such as antigenicity and toxicity analyses. The good water-soluble, non-toxic, probable antigenic, and DRB*0101 binder was selected. A multi-epitopes-based vaccine designing was then done where linkers were used to connect the shortlisted epitopes. In addition, an adjuvant molecule was supplementary to the multi-epitopes peptide to improve the vaccine’s immunogenic potential. The final vaccine construct’s three-dimensional structure was modeled by ab initio method. The vaccine molecule was then evaluated for its binding potential with TLR-3 immune receptor, which is key for its recognition and processing by the host immune system. Docking studies were performed using HADDOCK software. The best-docked complex was selected and visualized for intermolecular binding and interactions using UCSF Chimera 1.16 software. The findings revealed that the designed vaccine might be a potential vaccine against hantavirus and can be used in experimental animal model testings. Communicated by Ramaswamy H. Sarma

Emerging Maripa Hantavirus as a Potential Cause of a Severe Health Threat in French Guiana.

We describe the clinical parameters and management of nine confirmed cases of hantavirus pulmonary syndrome reported in French Guiana since 2008. All patients were admitted to Cayenne Hospital. Seven patients were men and the mean age was 48 years (range, 19-71 years). Two phases characterized the disease. The prodromal phase was characterized by fever (77.8%), myalgia (66.7%), and gastrointestinal symptoms (vomiting and diarrhea; 55.6%) starting, on average, 5 days before the illness phase, which was characterized by respiratory failure in all patients. Five patients died (55.6%) and the length of stay in the intensive care unit was 19 days (range, 11-28 days) for survivors. Detection of two back-to-back recent cases highlights the reason to screen for hantavirus infection during the nonspecific phase of the disease, in particular when concomitant pulmonary infection and digestive disorders are observed. Specific longitudinal serological surveys must also be used to identify other potential clinical forms of the disease in French Guiana.

Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission.

We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.

Deciphering the Hantavirus Host Range Combining Virology and Species Distribution Models with an Emphasis on the Yellow Pygmy Rice Rat (Oligoryzomys flavescens)

Hantaviruses are the causative agents of hantavirus pulmonary syndrome (HPS) in the Americas. In Central and South America, 28 hantavirus lineages were associated with different Sigmodontinae rodents. Of these, Lechiguanas hantavirus was initially described as a lineage associated with HPS cases in the central region of Argentina. Initial studies on the rodent hosts and viral lineages performed between 1999 and 2005 showed that HPS cases in Uruguay were distributed mostly in the southern region of the country, and that the Lechiguanas hantavirus (LECV) and the closely related Andes Central Plata hantaviruses were the viral lineages most frequently associated with HPS cases, both carried by the yellow pygmy rice rat (Oligoryzomys flavescens). Although these rodents are present all across the Uruguayan territory, determining the extent of the risk areas for hantavirus transmission based on the distribution of the infected rodents may be a useful tool for disease control and prevention. Distribution models are positioned as an effective instrument in the prediction of diseases affecting human health. Assessment of the potential distribution of rodent reservoir hosts and analysis of the influence of environmental factors on hantavirus transmission can help to understand the spatial patterns of disease transmission risk. In the present study, virological studies and species distribution models were integrated to understand the hantavirus infection risk pattern in Uruguay. Virological analyses confirmed that in Uruguay, the primary hantavirus reservoir host for both viral lineages is the yellow pygmy rice rat. Additionally, we report an Azara’s grass mouse (Akodon azarae) infected with the Andes Central Plata viral lineage. Based on the seropositive and nonseropositive yellow pygmy rice rats tested, the distribution models emphasized that favorable environmental conditions for the infected rodents are mainly related to the availability of human-disturbed rural environments with high humidity. We conclude that the innovative application of the methodologies reported herein allowed for the assessment of the current risk territory for HPS in Uruguay.

Hantavirus Infection in Children-A Pilot Study of Single Regional Center.

Hantaviruses are infectious etiological agents of a group of rodent-borne hemorrhagic fevers, with two types of clinical manifestations in humans: hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). According to available statistics, the disease occurs mainly in adults, but the lower incidence in the pediatric population might also be related to a lack of diagnosis possibilities or even unsatisfactory knowledge about the disease. The purpose of this study was to evaluate the cases of hemorrhagic fever with renal syndrome diagnosed and treated in the Department of Nephrology at St. Mary's Emergency Hospital for Children in Iasi, Romania, representative of the North-East of Romania. We also reviewed the specialized literature on the topic. Between January 2017 and January 2022, eight cases of HFRS, all men, and seven from rural areas, aged 11-18 years old, were referred to our clinic because of an acute kidney injury (AKI). Seven cases were identified as Dobrava serotype while one case was determined by Haantan serotype. HFRS should always be considered as a differential diagnosis when faced with a patient with AKI and thrombocytopenia. Dobrava serotype is the most common hantavirus subtype in the Balkans. For the specific prevention of human infections, mainly in high-risk groups, vaccines are needed. As far as we know, this is the first study on HFRS in Romanian children.

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.

Protocols to Prevent Transmission of the Hantavirus Pulmonary Syndrome: Three Case Studies

The goal of the paper is to explain the risk posed by rodent contaminated materials and environments to cultural heritage professionals, to provide sound information from professional literature and reputable sources, to offer standardized protocols gleaned from these sources, and to view the protocols through case studies from three projects. By spelling out the affinity that rodents have for historic sites, museum collections, archives holdings, records repositories, library collections, and cultural heritage infrastructure it will be clear the risk is paramount. By making clear the widespread habitat of rodents that can spread viruses the case is made for wide adoption of protocols. Diverse professionals, working in conservation and allied fields, can utilize information in this paper as a starting point in planning projects to assess, handle, and treat rodent impacted items, storage areas, and sites.

Hantavirus Pulmonary Syndrome: 1993-2018.

From 1993 to 2018, hantavirus infections were reported in 39 states, with hantavirus pulmonary syndrome (HPS) as the most common and fatal manifestation. To identify differences in the presentation of HPS between children and adults, we hypothesized that children with HPS would be diagnosed later in their illness course given the nonspecific clinical features of HPS. This was an evaluation of the clinical and demographic characteristics of national HPS cases from 1993 to 2018. Data were from the Centers for Disease Control and Prevention database and 1 state department of health, comprising 97% of US cases. We compared children (0 to 12 years), adolescents (13 to 18 years), and adults using nonparametric and parametric analyses, with additional exploratory analyses to identify clinical variables associated with mortality. Among 719 HPS patients, 22 (3.0%) were aged ≤12 years, 47 (6.5%) were 13 to 18 years old, and the remaining 650 (90.4%) were adults. Overall mortality was 35.4% and did not differ between age groups (P = .8). The time between symptom onset and death differed by age group, with children living a median of 2 days (interquartile range [IQR] 2 to 3), adolescents 4 days (IQR 3 to 5), and adults 5 days (IQR 4 to 8; P = .001). The mean highest hematocrit and median highest creatinine level were significantly associated with mortality in those 0 to 18 years old but not adults. In our dataset representing the largest study of HPS in the United States, we found that children with HPS died more quickly than adults and that highest hematocrit and creatinine levels were associated with death only among those <19 years old.

A Brief History of Bunyaviral Family Hantaviridae.

The discovery of Hantaan virus as an etiologic agent of hemorrhagic fever with renal syndrome in South Korea in 1978 led to identification of related pathogenic and nonpathogenic rodent-borne viruses in Asia and Europe. Their global distribution was recognized in 1993 after connecting newly discovered relatives of these viruses to hantavirus pulmonary syndrome in the Americas. The 1971 description of the shrew-infecting Hantaan-virus-like Thottapalayam virus was long considered an anomaly. Today, this virus and many others that infect eulipotyphlans, bats, fish, rodents, and reptiles are classified among several genera in the continuously expanding family Hantaviridae.

Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus

The emergence of Sin Nombre orthohantavirus, an etiological agent of hantavirus cardiopulmonary syndrome, exacerbates the situation and imposes a heavy financial burden on healthcare organizations. Multidrug-resistant forms of the disease are prevalent, and there is currently no licensed commercial vaccine. Due to the numerous limitations of experimental vaccines, vaccines against various bacterial and viral diseases have developed via computational vaccine design. Several subtractive proteomics, immunoinformatics, docking, and simulation approaches were used in this study to develop a multi-epitope-based vaccine against Sin Nombre orthohantavirus. One possible antigenic protein-the glycoprotein precursor of surface glycoproteins (accession number >AAC42202.1)-was selected as a candidate for B cell-derived T cell epitopes mapping the detailed analysis of the core genome. Among the predicted epitopes, four epitopes (QVDWTKKSST, GLAASPPHL, SSYSYRRKLV, and MESGWSDTA), which were probably antigenic, nonallergenic, nontoxic, and water soluble, were used in the multi-epitope vaccine's construction. The shortlisted epitopes have the potency to cover 99.78% of the world's population, 97.93% of the Chinese population, and 97.36% of the Indian population. The epitopes were connected through AAY linkers and joined with >50S ribosomal adjuvant to enhance their efficacy. The vaccine comprises 182 amino acids with a molecular weight of 19.03770 kDa and an instability index of 26.52, indicating that the protein is stable. A molecular docking study revealed that the vaccine has a good binding affinity with TLR-4 and TLR-8, which is vital for inducing the immune system. Top-1 docked complexes of vaccine- TLR-4 and TLR-8 with the lowest binding energy of -12.52 kc/mol and -5.42 kc/mol, respectively, were considered for molecular dynamic simulation analysis. Furthermore, we predicted that the docked complexes are properly stable throughout simulation time in both normal mode and AMBER-based simulation analysis. The MMGBSA analysis calculated -122.17 and -125.4 net binding energies for the TLR-8- and TLR4-vaccine complexes, respectively, while the MMPBSA analysis estimated -115.63 and -118.19 for the TLR-8- and TLR4-vaccine complex, respectively, confirming that the binding stability with receptors is stable, which is important for inducing a strong response. However, the current work is computation-based, so experimental validation is highly recommended.

Trends and focuses of hantavirus researches: a global bibliometric analysis and visualization from 1980 to 2020

BackgroundThere have been worldwide changes in the researches on hantaviruses in the past several decades. Nevertheless, there are few bibliometric analysis studies this field. We aim to evaluate and visualize the research focuses and trends of this field using a bibliometric analysis way to help understand the developmet and future hotspots of this field.Material and methodsPublications related to hantavirus studies were culled from the Web of Science Core Collection to generate trend analysis. The articles and reviews were re-extracted and Countries, institutions, authors, references and keywords in this field were visually analyzed by using VOSviewer and CiteSpace.ResultsA total of 4408 studies were included and the number of publications regarding hantaviruses significantly increased yearly. Three thousand seven hundred sixteen research articles and reviews were retrieved to generate bibliometric analysis. These studies mainly come from 125 countries led by USA and China and 3312 institutions led by the University of Helsinki. Twelve thousand five hundred twenty nine authors were identified and Vaheri A were the most influential author. Journal of Virology was the journal with the most studies and citations. After analysis, Hemorrhagic fever with renal syndrome, Hantavirus cardiopulmonary syndrome, nephropathia epidemica and related genotypes, clinical symptoms and rodents were the most common keywords and developing areas.ConclusionResearch on hantavirus is flourishing. Cooperation among different countries and institutions in this field must be strengthened in the future. The ecology and clinical symptoms of new genotypes, the vaccine development and factors that affect host population distribution and density are current and developing areas of study.