Hantavirus Pulmonary Syndrome Research Articles

Hantavirus pulmonary syndrome in patient with haemorragic fever with renal syndrome

Background: Hantaviruses cause in humans hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS holds a leading position in Russia among other natural focal infections. We present a clinical example of lung damage in a 39-year old patient with HFRS, a resident of the Republic of Mordovia. Case Description: The patient's illness started with a fever to 39.2 °C, chills, cough. He sought medical help two days after the symptoms onset. Lungs X-ray revealed signs of bilateral pneumonia. Cough with sputum, shortness of breath, crepitus in the left lung, slight increase of transaminases and small erythrocyturia were detected. Antiviral, antibacterial and supportive treatment was started, but the patient's condition deteriorated. Symptoms of the progressive shortness of breath and acute renal failure were appeared. Repeated X-ray of the lungs shown negative dynamics (an increase of the intensity of infiltration on both sides of lungs). Symptoms of respiratory failure (shortness of breath, weakened breathing), hemorrhagic syndrome (hematomas on the skin at the injection sites, extensive hemorrhages in the sclera of both eyes) were noted within 8 days of hospitalization. Symptoms of acute renal failure (pain in the lumbar area, repeated vomiting, oliguria) were observed, but laboratory manifestations of renal failure were mild (slight proteinuria and hematuria). Hemoconcentration, leukocytosis, thrombocytopenia were detected. Thoracic CT, ultrasound of the abdomen and kidneys determined the signs of polyserositis. Anti-Hantaan IgM 1:800 and Anti-Hantaan IgG – 1:800 weredetected in the indirect immunofluorescence reaction. The diagnosis of HFRS, severe course, HPS were diagnosed. 500 ml of transudate was removed from the pleural cavity during puncture of the right pleural cavity. Positive dynamics began to be observed from the 12th day of the disease: a decrease in the symptoms of intoxication and respiratory failure, free fluid was disappeared from the pleural and abdominal cavities. The patient was discharged on the 28th day of illness in a satisfactory condition. Discussion: Respiratory pathology usually does not play a major role in the clinical picture of HFRS, but recently it started to be more manifested. Conclusion: HFRS and HPS in rare cases can develop simultaneously in a patient with hantavirus infection

Hantavirus Cardiopulmonary Syndrome in Canada.

Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory disease caused by Sin Nombre virus in North America (SNV). As of January 1, 2020, SNV has caused 143 laboratory-confirmed cases of HCPS in Canada. We review critical aspects of SNV virus epidemiology and the ecology, biology, and genetics of HCPS in Canada.

Hantavirus pulmonary syndrome outbreaks associated with climate variability in Northwestern Argentina, 1997-2017.

BackgroundRodent-borne hantaviruses (genus Orthohantavirus) are the etiologic agents causing two human diseases: hemorrhagic fever with renal syndrome (HFRS) in Euroasia; and hantavirus pulmonary syndrome (HPS) in North and South America. In South America fatality rates of HPS can reach up to 35%–50%. The transmission of pathogenic hantaviruses to humans occurs mainly via inhalation of aerosolized excreta from infected rodents. Thus, the epidemiology of HPS is necessarily linked to the ecology of their rodent hosts and the contact with a human, which in turn may be influenced by climatic variability. Here we examined the relationship between climatic variables and hantavirus transmission aim to develop an early warning system of potential hantavirus outbreaks based on ecologically relevant climatic factors.Methodology and main findingsWe compiled reported HPS cases in northwestern Argentina during the 1997–2017 period and divided our data into biannual, quarterly, and bimestrial time periods to allow annual and shorter time delays to be observed. To evaluate the relationship of hantavirus transmission with mean temperature and precipitation we used dynamic regression analysis. We found a significant association between HPS incidence and lagged rainfall and temperature with a delay of 2 to 6 months. For the biannual and quarterly models, hantavirus transmission was positively associated with lagged rainfall and temperature; whereas the bimestrial models indicate a direct relationship with the rainfall but inverse for temperature in the second lagged period.Conclusions/SignificanceThis work demonstrates that climate variability plays a significant role in the transmission of hantavirus in northwestern Argentina. The model developed in this study provides a basis for the forecast of potential HPS outbreaks based on climatic parameters. Our findings are valuable for the development of public health policies and prevention strategies to mitigate possible outbreaks. Nonetheless, a surveillance program on rodent population dynamics would lead to a more accurate forecast of HPS outbreaks.

Diagnosis, Virology and Treatment for Hantavirus Pulmonary Syndrome (HPS): A Challenging Sickness to Human Health

Diagnosis, Virology and Treatment for Hantavirus Pulmonary Syndrome (HPS): A Challenging Sickness to Human Health

Cryofixation of Inactivated Hantavirus-Infected Cells as a Method for Obtaining High-Quality Ultrastructural Preservation for Electron Microscopic Studies.

Hantaviruses rewire the host cell and induce extensive membrane rearrangements for their replication and the morphogenesis of the virion. Transmission electron microscopy (TEM) is a powerful technique for imaging these pathological membrane changes especially when combined with large volume electron tomography. Excellent preservation of membrane structure can be obtained when chemical fixation is combined with cryofixation via high pressure freezing making the samples amenable to serial-section tomographic reconstruction. Taking advantage of this, we have optimized a hybrid method that employs aldehyde fixation, a step that is essential for virus inactivation, followed by high-pressure freezing for ultrastructural study of Hantaan (HTN) and Andes (AND) virus infected Vero E6 cells. HTNV and ANDV are two species of the Orthohantavirus, from the Old and New World, respectively, and the causative agents of hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome in humans. We applied the method for the qualitative assessment of the perturbation of the endomembrane system induced by HTNV and ANDV in infected vs. mock-infected cells. Screening of serial-sections revealed consistency of membrane preservation across large volumes indicating potential of these samples for tomographic studies. Images revealed large-scale perturbations of the endomembrane system following HTNV-infection that included the dilation of the rough endoplasmic reticulum and fragmentation of the Golgi apparatus. Infected cells exhibited a tendency to accumulate large numbers of vacuoles that were especially apparent in ANDV. In summary, our hybrid method provides a path for the study of BSL-3 pathogens using cutting edge 3D-imaging technologies.

Hantavirus Infection Is Inhibited by Griffithsin in Cell Culture.

Andes virus (ANDV) and Sin Nombre virus (SNV), highly pathogenic hantaviruses, cause hantavirus pulmonary syndrome in the Americas. Currently no therapeutics are approved for use against these infections. Griffithsin (GRFT) is a high-mannose oligosaccharide-binding lectin currently being evaluated in phase I clinical trials as a topical microbicide for the prevention of human immunodeficiency virus (HIV-1) infection (ClinicalTrials.gov Identifiers: NCT04032717, NCT02875119) and has shown broad-spectrum in vivo activity against other viruses, including severe acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, and Nipah virus. In this study, we evaluated the in vitro antiviral activity of GRFT and its synthetic trimeric tandemer 3mGRFT against ANDV and SNV. Our results demonstrate that GRFT is a potent inhibitor of ANDV infection. GRFT inhibited entry of pseudo-particles typed with ANDV envelope glycoprotein into host cells, suggesting that it inhibits viral envelope protein function during entry. 3mGRFT is more potent than GRFT against ANDV and SNV infection. Our results warrant the testing of GRFT and 3mGRFT against ANDV infection in animal models.

Characterization of Oral Immunity in Cases and Close Household Contacts Exposed to Andes Orthohantavirus (ANDV)

Background: Andes orthohantavirus (ANDV) is the sole etiologic agent of Hantavirus Cardiopulmonary Syndrome in Chile and, until now, the only Hantavirus known to be transmitted by person-to-person route. The main risk of person-to-person transmission is to be a sexual partner of an index case, and deep kissing the main mechanism of infection. Experimental reports suggest that ANDV infection can be inhibited by some saliva components. Therefore, some host factors like saliva quality, could help to explain why some individuals do not become infected even though their exposure to the virus is high.Aim: To compare some saliva components, such cytokines and mucins, between ANDV-infected cases (exposed-sick), their close household contacts (exposed-not sick) and healthy control not exposed.Methods: Sixty-nine confirmed ANDV-infected cases, 76 close household contacts exposed to ANDV but not infected (CHC) and 39 healthy control not exposed (HCNE). The following components were measured in saliva: secretory immunoglobulin A (sIgA) by ELISA; cytokines (IL1β, IL12p70, TNFα, INFy, IL10, IL6, VEGF, IP10, and IL8) by Multiplex Assay and mucins MUC7 and MUC5B by Western Blotting.Results: Among infected cases, CHC and HCNE analyzed 74, 45, and 33% were men, respectively (p ≤ 0.05). The average age for cases, CHC and HCNE was 37.7, 28.7, and 32 years, respectively (p ≤ 0.05). The average concentration of sIgA in infected cases was 4.846 mg/mL, higher than for CHC group, 0.333 mg/mL (p ≤ 0.05). For cytokines, significant differences were found comparing all groups for IFNy, IL12p70, and IL8. Among CHC group, there was a higher frequency of detection of MUC7 isoform (62.6%; 31/49) compared to ANDV-infected cases (40.5%; 17/42) (p < 0.05). Similarly, presence of MUC5B was higher among CHC groups (62.16%; 46/74) than in ANDV-infected cases (44.4%; 28/63) (p < 0.05).Conclusions: Three salivary components showed differences between infected cases and close household contacts (sIgA, cytokines, and mucins). These differences can be explained by the acute state of the disease in the ANDV-infected cases group. However, the differences in MUC5B and isoforms of MUC7 are not entirely explainable by the infection itself. This work represents a novel description of salivary components in the context of ANDV infection.

Hantavirus Infections-Treatment and Prevention.

Purpose of reviewHantavirus infection is an emerging zoonosis and there are two main clinical presentations, hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS). Although Hantavirus infections have a worldwide distribution with a high mortality rate, a safe and effective vaccine or an antiviral drug against the Hantavirus disease is yet to be available. This review summarizes all the efforts undertaken to develop medical countermeasures in vitro, in vivo, and human clinical trials against Hantavirus infections.Recent findingsMultiple antivirals are shown to be effective with limited evidence and recent studies on immunotherapy were not very conclusive. There are multiple vaccine candidates with evidence of conferring long protective immunity against Hantaviruses. Some of these had been already trialed on humans.SummaryAt present, severe HPS or HFRS case management is purely based on supportive treatments, often in an intensive care unit. Rodent control and public health education and promotion play a major role in preventing Hantavirus infection.

HANTAVIRUS CARDIOMYOPATHY IN A PATIENT WITH NEWLY DIAGNOSED SYSTEMIC LUPUS ERYTHEMATOSUS

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Hantavirus infection, traditionally associated with Hantavirus Pulmonary Syndrome in critically ill adults, has been described in less severe illness with resultant cardiopulmonary consequences, particularly in strains endemic to Texas. Characterized by pulmonary infiltrates and azotemia, cardiomyopathy is a feared complication of acute disease. Systemic Lupus Erythematosus (SLE), a pathology of diffuse inflammation, may serve as a predisposition to the development of viral sequelae. CASE PRESENTATION: A 37-year-old healthy female with occupational lumber exposure presented with one week of persistent, positional and pleuritic pain and dyspnea following self-limited upper respiratory symptoms.She was afebrile and hypertensive (140/100) with tachycardia (102) and ambulatory pulse oximetry 88%. Auscultation was limited due to pain with inspiration but exam yielded no murmurs or rubs. Electrocardiogram revealed no PR or ST segment changes and CT angiogram demonstrated bilateral ground glass opacities and reactive lymphadenopathy without pulmonary embolism.Laboratory analysis returned significant for creatinine 1.28, albumin 2.7, troponin <.03, negative HIV and respiratory virus panel and normal complements. Urine studies had subnephrotic range proteinuria without casts. Serologic studies reported ANA >1:2560, elevated RNP, Rheumatoid Factor, Smith and SS-A antibodies and positive IgM testing for hantavirus. Echocardiogram verified an ejection fraction of 25-30% without pericardial effusion. Coronary and pulmonary artery catheterization were negative for ischemic heart disease or pulmonary hypertension. DISCUSSION: She was treated with colchicine, prednisone and furosemide with improvement. Given the presence of specific antibodies, negative cardiac catheterization, characteristic echocardiographic findings and clear viral trigger, the patient was clinically diagnosed with hantavirus cardiomyopathy in the setting of newly diagnosed SLE serving as a predisposition to a worsening inflammatory cascade. Due to high pretest probability and invasive nature of the procedure, endomyocardial biopsy was deferred. Ejection fraction recovered after three months following therapy with carvedilol and lisinopril. Hantavirus has been described as a precipitant of functional, often reversible, cardiomyopathy without myocardial structure disruption. Given the rapid return of cardiac function following guideline directed medical optimization, we posit a significant viral contribution. CONCLUSIONS: This case contributes to the body of literature identifying hantavirus as a cause of functional cardiomyopathy. In the setting of co-morbid SLE, it lends to the importance of considering infectious etiologies in tandem with underlying inflammatory physiology. We believe the incidence of hantavirus to be underreported and must be considered in a patient with pulmonary infiltrates, renal involvement and cardiomyopathy. Reference #1: Knust B, Rollin PE. Twenty-year summary of surveillance for human hantavirus infections, United States. Emerg Infect Dis. 2013;19(12):1934–1937 Reference #2: Fabiano P. Saggioro, Marcos A. Rossi, Maria Irma S. Duarte, Carmen Cinira S. Martin, Venâncio A. F. Alves, Marcos L. Moreli, Luis Tadeu M. Figueiredo, Jorge E. Moreira, Alessandra A. Borges, Luciano Neder, Hantavirus Infection Induces a Typical Myocarditis That May Be Responsible for Myocardial Depression and Shock in Hantavirus Pulmonary Syndrome, The Journal of Infectious Diseases, Volume 195, Issue 10, 15 May 2007, Pages 1541–1549, https://doi.org/10.1086/513874 Reference #3: Machado, A. M., De Figueiredo, G. G., Sabino dos Santos Jr, G., & Figueiredo, L. T. M. (2009). Laboratory diagnosis of human hantavirus infection: novel insights and future potential. Future Virology, 4(4), 383-389. DISCLOSURES: No relevant relationships by Molly Horstman, source=Web Response No relevant relationships by Christopher Nemeh, source=Web Response No relevant relationships by Thiennga Vo, source=Web Response

Hantavirus diseases pathophysiology, their diagnostic strategies and therapeutic approaches: A review.

Hantaviruses are enveloped negative (-) single-stranded RNA viruses belongs to Hantaviridae family, hosted by small rodents and entering into the human body through inhalation, causing haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) also known as hantavirus cardiopulmonary syndrome (HCPS). Hantaviruses infect approximately more than 200000 people annually all around the world and its mortality rate is about 35%-40%. Hantaviruses play significant role in affecting the target cells as these inhibit the apoptotic factor in these cells. These viruses impair the integrity of endothelial barrier due to an excessive innate immune response that is proposed to be central in the pathogenesis and is a hallmark of hantavirus disease. A wide range of different diagnostic tools including polymerase chain reaction (PCR), focus reduction neutralization test (FRNT), enzyme-linked immunosorbent assay (ELISA), immunoblot assay (IBA), immunofluorescence assay (IFA), and other molecular techniques are used as detection tools for hantavirus in the human body. Now the availability of therapeutic modalities is the major challenge to control this deadly virus because still no FDA approved drug or vaccine is available. Antiviral agents, DNA-based vaccines, polyclonal and monoclonal antibodies neutralized the viruses so these techniques are considered as the hope for the treatment of hantavirus disease. This review has been compiled to provide a comprehensive overview of hantaviruses disease, its pathophysiology, diagnostic tools and the treatment approaches to control the hantavirus infection.

Associação entre síndrome cardiopulmonar do hantavírus em humanos e configuração da paisagem na região do Cerrado de Minas Gerais, Brasil

The objective of this study was to analyze the spatiotemporal distribution of 193 autochthonous cases that were confirmed as hantavirus cardiopulmonary syndrome (HCPS) from 1998 to 2007 and its association with landscape configuration in the Cerrado region of Minas Gerais, Brazil. Among the 193 autochthonous cases, the probable sites of infection (PSI) of 129 cases (66.8%) were geoprocessed. We then evaluated the association between the HCPS cases and landscape variables through a multivariate analysis of the main components. Particularly, the mesoregion of Triângulo Mineiro/Alto Paranaiba had 130 autochthonous cases (67.3%). In addition, the chance of conglomeration of cases in municipalities located in this mesoregion was greater than that in other mesoregions. HCPS cases were positively associated with the increase in the area of planted pastures and natural forests in the Cerrado region. Rice, beans, maize, and sugar cane cultivations were less associated with HCPS. We concluded that the changes in the Cerrado ecosystem due to agricultural activities propitiate the maintenance of rodent populations and HCPS virus reservoirs. Additional training for health professionals for early diagnosis and reduction of the causes of the disease must be carried out in the endemic areas of Minas Gerais.

Orthohantaviruses, Emerging Zoonotic Pathogens.

Orthohantaviruses give rise to the emerging infections such as of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in Eurasia and the Americas, respectively. In this review we will provide a comprehensive analysis of orthohantaviruses distribution and circulation in Eurasia and address the genetic diversity and evolution of Puumala orthohantavirus (PUUV), which causes HFRS in this region. Current data indicate that the geographical location and migration of the natural hosts can lead to the orthohantaviruses genetic diversity as the rodents adapt to the new environmental conditions. The data shows that a high level of diversity characterizes the genome of orthohantaviruses, and the PUUV genome is the most divergent. The reasons for the high genome diversity are mainly caused by point mutations and reassortment, which occur in the genome segments. However, it still remains unclear whether this diversity is linked to the disease’s severity. We anticipate that the information provided in this review will be useful for optimizing and developing preventive strategies of HFRS, an emerging zoonosis with potentially very high mortality rates.

Comparison of VSV Pseudovirus and Focus Reduction Neutralization Assays for Measurement of Anti-Andes orthohantavirus Neutralizing Antibodies in Patient Samples.

Andes orthohantavirus (ANDV) is the etiologic agent of hantavirus cardiopulmonary syndrome (HCPS), which has a case fatality rate around 35%, with no effective treatment or vaccine available. ANDV neutralizing antibody (NAb) measurements are important for the evaluation of the immune response following infection, vaccination, or passive administration of investigational monoclonal or polyclonal antibodies. The standard assay for NAb measurement is a focus reduction neutralization test (FRNT) featuring live ANDV and must be completed under biosafety level (BSL)-3 conditions. In this study, we compared neutralization assays featuring infectious ANDV or vesicular stomatitis virus (VSV) pseudovirions decorated with ANDV glycoproteins for their ability to measure anti-ANDV NAbs from patient samples. Our studies demonstrate that VSV pseudovirions effectively measure NAb from clinical samples and have greater sensitivity compared to FRNT with live ANDV. Importantly, the pseudovirus assay requires less labor and sample materials and can be conducted at BSL-2.

Differential CD4 T Regulatory Cell Phenotype Induced by Andes Hantavirus Glycoprotein.

Hantavirus cardiopulmonary syndrome (HCPS) caused by Andes orthohantavirus (ANDV) in South America is a public health threat due to the significant rate of mortality and the lack of a specific treatment. Interestingly, the virus does not produce cytopathic effect, thereby the strong antiviral immune response is suspected to contribute to pathogenesis, hence is important to understand the balance between protective and harmfully immunity. CD4+ T regulatory cells (Treg) are essential to control an exacerbated immune response. In human ANDV infection, little is known about CD4+ Treg cells, which may be involved in control immunopathology associated to the infection. In this report, we characterize the phenotype of memory CD4+ Tregs in a HCPS survivor's cohort. Based on the expression of CXCR3, CCR4, and CCR6, we identified different Th-like Treg populations in ANDV survival's PBMCs. In addition, the effect of ANDV-glycoprotein virus like particles (VLP) was determined. We demonstrated that memory CD4+ Treg from HCPS present a specific phenotype, showing higher frequency of PD-1 compared to healthy donors (HD). In addition, it was observed a decrease in the frequency of Th1-like memory CD4+ Treg in HCPS, important to highlight that this signature could be preserved even years after resolution of infection. Moreover, to gain insight in the mechanism involved, we evaluated whether ANDV-glycoprotein (GP) VLP could modulate CD4+ Treg. Interestingly, ANDV-GP VLP induced a decrease in the frequency of CXCR3 (Th1-like) and an increase in CCR4 (Th2-like) memory CD4+ Treg in both HD and HCPS PBMCs, indicating that ANDV-GP could specifically act over CXCR3 and CCR4 in CD4+ Treg. This report contributes to the study of human CD4+ Treg cells in ANDV infection.

Moving to healthier landscapes: Forest restoration decreases the abundance of Hantavirus reservoir rodents in tropical forests

Hantavirus Cardiopulmonary Syndrome (HCPS) is a disease with high human lethality rates, whose transmission risk is directly related to the abundance of reservoir rodents. In the Brazilian Atlantic forest, the main reservoirs species, Oligoryzomys nigripes and Necromys lasiurus, are thought to increase in abundance with deforestation. Therefore, forest restoration may contribute to decrease HCPS transmission risk, a topic still unexplored, especially in tropical regions. Aiming at filling this research gap, we quantified the potential of forest restoration, as required by the current environmental legislation, to reduce the abundance of Hantavirus reservoir rodents in the Brazilian Atlantic Forest. Using a dataset on small mammal communities sampled at 104 sites, we modeled how the abundance of these two rodent species change with the percentage of forest cover and forest edge density. From the best model, we extrapolated rodent abundance to the entire Atlantic Forest, considering two scenarios: current and restored forest cover. Comparing the estimated abundance between these two scenarios, we show that forest restoration can reduce the abundance of O. nigripes up to 89.29% in 43.43% of Atlantic forest territory. For N. lasiurus, abundance decreased up to 46% in 44% of the Atlantic forest. To our knowledge, this is the first study linking forest restoration and zoonotic diseases. Our results indicate that forest restoration would decrease the chance of HCPS transmission in ~45% of the Atlantic forest, making the landscape healthier to ~2,8 million people living within this area. This positive effect of restoration on disease regulation should be considered as an additional argument to encourage and promote forest restoration in tropical areas around the world.

Biodefense Implications of New-World Hantaviruses.

Hantaviruses, part of the Bunyaviridae family, are a genus of negative-sense, single-stranded RNA viruses that cause two major diseases: New-World Hantavirus Cardiopulmonary Syndrome and Old-World Hemorrhagic Fever with Renal Syndrome. Hantaviruses generally are found worldwide with each disease corresponding to their respective hemispheres. New-World Hantaviruses spread by specific rodent-host reservoirs and are categorized as emerging viruses that pose a threat to global health and security due to their high mortality rate and ease of transmission. Incidentally, reports of Hantavirus categorization as a bioweapon are often contradicted as both US National Institute of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention refer to them as Category A and C bioagents respectively, each retaining qualitative levels of importance and severity. Concerns of Hantavirus being engineered into a novel bioagent has been thwarted by Hantaviruses being difficult to culture, isolate, and purify limiting its ability to be weaponized. However, the natural properties of Hantaviruses pose a threat that can be exploited by conventional and unconventional forces. This review seeks to clarify the categorization of Hantaviruses as a bioweapon, whilst defining the practicality of employing New-World Hantaviruses and their effect on armies, infrastructure, and civilian targets.

Orthohantavirus Pathogenesis and Cell Tropism.

Orthohantaviruses are zoonotic viruses that are naturally maintained by persistent infection in specific reservoir species. Although these viruses mainly circulate among rodents worldwide, spill-over infection to humans occurs. Orthohantavirus infection in humans can result in two distinct clinical outcomes: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). While both syndromes develop following respiratory transmission and are associated with multi-organ failure and high mortality rates, little is known about the mechanisms that result in these distinct clinical outcomes. Therefore, it is important to identify which cell types and tissues play a role in the differential development of pathogenesis in humans. Here, we review current knowledge on cell tropism and its role in pathogenesis during orthohantavirus infection in humans and reservoir rodents. Orthohantaviruses predominantly infect microvascular endothelial cells (ECs) of a variety of organs (lungs, heart, kidney, liver, and spleen) in humans. However, in this review we demonstrate that other cell types (e.g., macrophages, dendritic cells, and tubular epithelium) are infected as well and may play a role in the early steps in pathogenesis. A key driver for pathogenesis is increased vascular permeability, which can be direct effect of viral infection in ECs or result of an imbalanced immune response in an attempt to clear the virus. Future studies should focus on the role of identifying how infection of organ-specific endothelial cells as well as other cell types contribute to pathogenesis.

Oral Vaccination With Recombinant Vesicular Stomatitis Virus Expressing Sin Nombre Virus Glycoprotein Prevents Sin Nombre Virus Transmission in Deer Mice.

Sin Nombre virus (SNV) is the major cause of hantavirus cardiopulmonary syndrome (HCPS) in North America, a severe respiratory disease with a high fatality rate. SNV is carried by Peromyscus maniculatus, or deer mice, and human infection occurs following inhalation of aerosolized virus in mouse excreta or secreta, often in peri-domestic settings. Currently there are no FDA approved vaccines or therapeutics for SNV or any other hantaviruses, therefore prevention of infection is an important means of reducing the disease burden of HCPS. One approach for preventing HCPS cases is to prevent the spread of the virus amongst the rodent reservoir population through bait vaccination. However, bait style vaccines for rodent-borne viruses have not been employed in the field, unlike those targeting larger species. Here we utilized a recombinant vesicular stomatitis virus expressing SNV glycoprotein precursor (rVSVΔG/SNVGPC) in an attempt to prevent SNV transmission. Vaccination of deer mice with rVSVΔG/SNVGPC was able to reduce viral RNA copy numbers in the blood and lungs of directly infected animals. More importantly, vaccination, either intramuscularly or orally, significantly reduced the number of transmission events in a SNV transmission model compared with control animals. This provides a proof-of-concept in which oral vaccination of deer mice results in protection against acquiring the virus following direct contact with infected deer mice. Further development of bait style vaccines for SNV or other rodent-borne viruses could provide an effective means of reducing disease burden.

Molecular characters of Hantaviruses, epidemiology and pathogenicity

The year 2020 has indeed been a year of crisis after the outbreak of Novel Corona virus there was another virus that showed its presence, it was Hantavirus. Several Chinese news channels reported death of a man due to hanta virus and the other 32 people were tested along, those who were in contact. There was indeed a risk of another outbreak while the whole world was still suffering from the COVID-19 crisis. Several novel Hantaviruses with unknown pathogenic potential have been identified in a variety of insectivore hosts. With the new hosts, new geographical distributions of Hantaviruses have also been discovered and several new species were found in Africa. Hantavirus infection in humans can result in two clinical syndromes: haemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS) caused by Old World and New World hantaviruses, respectively. This review focuses on the molecular properties of Hantaviruses that were found in the recent outbreaks, with a focus on epidemiology, the pathogenicity is described in relation to human as a host also diagnostic and possible treatment approaches have been described, microbiology remains a choice of interest as it is important to know complete structural components of the virus in order to tackle and block the lethal pathogenic abilities. The pathogenesis is likely to be a complex multifactorial process that includes contributions from immune responses, platelet dysfunction and the deregulation of endothelial cell barrier functions. This review summarizes recent data documenting interactions established by pathogenic Hantaviruses with their natural or human hosts that could highlight their different outcomes.

Atypical case of hantavirus infection in Sri Lanka mimicking leptospirosis: a case report

BackgroundHantavirus infection is an emerging zoonotic infection which has two characteristic patterns of presentation: hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. The clinical presentation of hantavirus infection closely mimics leptospirosis.Case presentationThis case report describes a previously apparently well 36-year-old Sri Lankan Sinhalese man who presented with an acute febrile illness with myalgia, with liver involvement in the form of transaminitis, cardiac involvement in the form of myocarditis, acute kidney injury, and pulmonary involvement. He was initially managed as severe leptospirosis with multiorgan dysfunction with antibiotics, steroids, and N-acetyl cysteine. A diagnosis of acute hantavirus infection was made subsequently. He made an uneventful recovery.ConclusionHantavirus infections need to considered in the differential diagnosis of patients presenting with acute febrile illness with multiorgan involvement. Larger studies are needed to evaluate the seroprevalence of hantavirus in Sri Lanka because it could be an emerging serious public health problem.