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Clinical Microbiology and Infection :... Apr 2019Over the past few decades understanding and recognition of hantavirus infection has greatly improved worldwide, but both the amplitude and the magnitude of hantavirus... (Review)
Review
Over the past few decades understanding and recognition of hantavirus infection has greatly improved worldwide, but both the amplitude and the magnitude of hantavirus outbreaks have been increasing. 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. The clinical presentation of HFRS varies from subclinical, mild, and moderate to severe, depending in part on the causative agent of the disease. In general, HFRS caused by Hantaan virus, Amur virus and Dobrava virus are more severe with mortality rates from 5 to 15%, whereas Seoul virus causes moderate and Puumala virus and Saaremaa virus cause mild forms of disease with mortality rates <1%. The central phenomena behind the pathogenesis of both HFRS and HCPS are increased vascular permeability and acute thrombocytopenia. 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. Also a genetic predisposition, related to HLA type, seems to be important for the severity of the disease. As there is no effective treatment or vaccine approved for use in the USA and Europe, public awareness and precautionary measures are the only ways to minimize the risk of hantavirus disease.
Topics: Animals; Disease Outbreaks; Disease Reservoirs; Orthohantavirus; Hantavirus Infections; Hantavirus Pulmonary Syndrome; Hemorrhagic Fever with Renal Syndrome; Humans
PubMed: 24750436
DOI: 10.1111/1469-0691.12291 -
Viruses Jul 2019Hantaviruses, members of the order , family , have a world-wide distribution and are responsible for greater than 150,000 cases of disease per year. The spectrum of... (Review)
Review
Hantaviruses, members of the order , family , have a world-wide distribution and are responsible for greater than 150,000 cases of disease per year. The spectrum of disease associated with hantavirus infection include hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) also known as hantavirus cardiopulmonary syndrome (HCPS). There are currently no FDA-approved vaccines or treatments for these hantavirus diseases. This review provides a summary of the status of vaccine and antiviral treatment efforts including those tested in animal models or human clinical trials.
Topics: Adrenal Cortex Hormones; Amides; Animals; Antiviral Agents; Clinical Trials as Topic; Orthohantavirus; Hantavirus Infections; Hantavirus Pulmonary Syndrome; Hemorrhagic Fever with Renal Syndrome; Humans; Immunotherapy; Lactoferrin; Models, Animal; Nucleosides; Piperidines; Pyrazines; Quinazolines; Recombinant Proteins; Ribavirin; Triazoles; Vaccines, Synthetic; Viral Vaccines
PubMed: 31277410
DOI: 10.3390/v11070610 -
Virologica Sinica Jun 2021Hantavirus infection is a global health challenge, causing widespread public concern. In recent years, cases of hantavirus infection in pregnant women have been reported... (Review)
Review
Hantavirus infection is a global health challenge, causing widespread public concern. In recent years, cases of hantavirus infection in pregnant women have been reported in many countries. The infected pregnant women and their fetuses appear to have more severe clinical symptoms and worse clinical outcomes. Hence, to study the prevalence of hantavirus infection in pregnant women, this study will focus on the epidemiological distribution of the virus, different virus species penetrating the placental barrier, and factors affecting the incidence and clinical outcome of the infection in pregnant women and their fetuses. In addition, this review will also discuss the diagnostic tools and treatments for pregnant patients and provide an overview of the relevant future research.
Topics: Female; Humans; Pregnancy; Amplified Fragment Length Polymorphism Analysis; Cesarean Section; Hantavirus Infections; Orthohantavirus; Placenta
PubMed: 33074475
DOI: 10.1007/s12250-020-00300-8 -
MSphere Jul 2020Hantaviruses are zoonotic pathogens found in parts of Europe, Asia, South America, and North America, which can cause renal and respiratory failure with fatality rates... (Review)
Review
Hantaviruses are zoonotic pathogens found in parts of Europe, Asia, South America, and North America, which can cause renal and respiratory failure with fatality rates up to 40%. There are currently no FDA-approved vaccines or therapeutics for hantavirus-related diseases; however, it is evident that a robust neutralizing antibody response is critical for protection from severe disease. Although virologists first described this family of viruses in the 1950s, there is limited information on the neutralizing epitopes that exist on the hantavirus antigenic glycoproteins, Gn and Gc, and sites important for the design of effective therapeutics and vaccines. We provide a thorough summary of the hantavirus field from an immunological perspective. In particular, we discuss our current structural knowledge of antigenic proteins Gn and Gc, identification of B cell neutralizing epitopes, previously isolated monoclonal antibodies and their cross-reactivity between different hantavirus strains, and current developments toward vaccines and therapeutics. We conclude with some outstanding questions in the field and emphasize the need for additional studies of the human antibody response to hantavirus infection. Hantaviruses are pathogens that sometimes pass from animals to humans, and they are found in parts of Europe, Asia, and North and South America. When human infection occurs, these viruses can cause kidney or lung failure, and as many as 40% of infected people die. Currently, there are no vaccines or therapeutics for hantavirus-related diseases available. A first step in developing prevention measures is determining what type of immune response is protective. Increasingly it has become clear that the induction of a type of response called a neutralizing antibody response is critical for protection from severe disease. Although virologists first described this family of viruses in the 1950s, there is limited information on what features on the surface of hantaviruses are recognized by the immune system. Here, we review the current state of knowledge of this information, which is critical for the design of effective therapeutics and vaccines.
Topics: Animals; Antibodies, Neutralizing; Antigens, Viral; Clinical Trials as Topic; Epitopes, B-Lymphocyte; Orthohantavirus; Hantavirus Infections; Humans; Immunity, Humoral; Mice
PubMed: 32669473
DOI: 10.1128/mSphere.00482-20 -
Viruses Dec 2021Annually, over 10,000 cases of hemorrhagic fever with renal syndrome (HFRS) are diagnosed in Europe. Puumala hantavirus (PUUV) causes most of the European HFRS cases.... (Review)
Review
Annually, over 10,000 cases of hemorrhagic fever with renal syndrome (HFRS) are diagnosed in Europe. Puumala hantavirus (PUUV) causes most of the European HFRS cases. PUUV causes usually a relatively mild disease, which is rarely fatal. However, the severity of the infection varies greatly, and factors affecting the severity are mostly unrevealed. Host genes are known to have an effect. The typical clinical features in PUUV infection include acute kidney injury, thrombocytopenia, and increased vascular permeability. The primary target of hantavirus is the endothelium of the vessels of different organs. Although PUUV does not cause direct cytopathology of the endothelial cells, remarkable changes in both the barrier function of the endothelium and the function of the infected endothelial cells occur. Host immune or inflammatory mechanisms are probably important in the development of the capillary leakage. Several immunoinflammatory biomarkers have been studied in the context of assessing the severity of HFRS caused by PUUV. Most of them are not used in clinical practice, but the increasing knowledge about the biomarkers has elucidated the pathogenesis of PUUV infection.
Topics: Acute Kidney Injury; Antibodies, Viral; Biomarkers; Cytokines; Endothelial Cells; Europe; Orthohantavirus; Hantavirus Infections; Hemorrhagic Fever with Renal Syndrome; Humans; Puumala virus; Thrombocytopenia
PubMed: 35062248
DOI: 10.3390/v14010045 -
Revue Scientifique Et Technique... Apr 2000Hantaviruses are the causative agents of the zoonotic diseases known as haemorrhagic fever with renal syndrome (HFRS) in Europe and Asia, and hantavirus pulmonary... (Review)
Review
Hantaviruses are the causative agents of the zoonotic diseases known as haemorrhagic fever with renal syndrome (HFRS) in Europe and Asia, and hantavirus pulmonary syndrome (HPS) in the Americas. These pathogens are maintained in the wild by rodent reservoirs and are mainly transmitted via the aerosol route. The infection is chronic and apparently asymptomatic in host animals. Whilst HFRS is caused by Hantaan, Seoul, Dobrava and Puumala hantaviruses, HPS is associated with Sin Nombre-like viruses. Common clinical features of HFRS and HPS include fever, myalgia, thrombocytopenia, leukocytosis and a capillary leak syndrome associated with shock in most severe cases. Outbreaks of HFRS and HPS are generally observed during years with dense rodent populations resulting from favourable climatic and environmental conditions. Human activities, such as rodent trapping, farming, cleaning rodent-infested areas, construction work, camping and hunting, are also implicated in the occurrence of hantavirus disease. Prophylactic measures in endemic areas rely essentially on information campaigns and rodent control.
Topics: Americas; Animals; Asia; Disease Outbreaks; Disease Reservoirs; Europe; Hantavirus Infections; Humans; Rodent Control; Rodentia; Zoonoses
PubMed: 11189727
DOI: 10.20506/rst.19.1.1209 -
Viruses Sep 2019Rapid point-of-care testing is a megatrend in infectious disease diagnosis. We have introduced a homogeneous immunoassay concept, which is based on the simultaneous...
Rapid point-of-care testing is a megatrend in infectious disease diagnosis. We have introduced a homogeneous immunoassay concept, which is based on the simultaneous binding of antigen and protein L to a given immunoglobulin molecule. The complex formation is detected utilizing time-resolved Förster resonance energy transfer between antigen-attached donor and acceptor-labeled protein L, hence the name LFRET. Here, we demonstrate that urine can be used as a sample matrix in LFRET-based serodiagnostics. We studied urine samples collected during the hospitalization and recovery of patients with acute Puumala orthohantavirus (PUUV) infection. We compared PUUV antibody-specific LFRET signals in urine to those in plasma, and found excellent correlation in the test outcomes The LFRET test from urine was positive in 40/40 patients with acute PUUV infection. PUUV causes a mild form of hemorrhagic fever with renal syndrome, characterized by acute kidney injury and proteinuria. Immunofluorescence and western blotting demonstrated PUUV-IgG and -IgA in urine, however, the presence of intact immunoglobulins did not fully explain the LFRET signals. We purified free light chains (FLCs) from both urine and serum of healthy volunteers and patients with acute PUUV infection, and verified the presence of antigen-specific FLCs. Antigen-specific FLCs provide a new means for non-invasive antibody detection and disease diagnosis.
Topics: Antibodies, Viral; Capsid Proteins; Orthohantavirus; Hantavirus Infections; Hemorrhagic Fever with Renal Syndrome; Humans; Immunoassay; Immunoglobulin A; Immunoglobulin G; Immunoglobulin Light Chains; Point-of-Care Testing; Puumala virus; Serologic Tests; Viral Core Proteins
PubMed: 31480594
DOI: 10.3390/v11090809 -
Virologica Sinica Feb 2017Hantaviruses are comprised of tri-segmented negative sense single-stranded RNA, and are members of the Bunyaviridae family. Hantaviruses are distributed worldwide and... (Review)
Review
Hantaviruses are comprised of tri-segmented negative sense single-stranded RNA, and are members of the Bunyaviridae family. Hantaviruses are distributed worldwide and are important zoonotic pathogens that can have severe adverse effects in humans. They are naturally maintained in specific reservoir hosts without inducing symptomatic infection. In humans, however, hantaviruses often cause two acute febrile diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). In this paper, we review the epidemiology and epizootiology of hantavirus infections worldwide.
Topics: Animals; Disease Reservoirs; Global Health; Orthohantavirus; Hantavirus Pulmonary Syndrome; Hemorrhagic Fever with Renal Syndrome; Humans; Zoonoses
PubMed: 28120221
DOI: 10.1007/s12250-016-3899-x -
Frontiers in Cellular and Infection... 2020Orthohantaviruses are zoonotic viruses that are naturally maintained by persistent infection in specific reservoir species. Although these viruses mainly circulate among... (Review)
Review
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.
Topics: Endothelial Cells; Orthohantavirus; Hantavirus Infections; Hemorrhagic Fever with Renal Syndrome; Humans; Tropism
PubMed: 32903721
DOI: 10.3389/fcimb.2020.00399 -
Current Opinion in Virology Oct 2021Hantaviruses are rodent-borne viruses distributed worldwide, transmitted through the air and with the ability to spread from person to person. They maintain a... (Review)
Review
Hantaviruses are rodent-borne viruses distributed worldwide, transmitted through the air and with the ability to spread from person to person. They maintain a non-symptomatic persistent infection in their rodent hosts, but their spillover to humans produces a renal or pulmonary syndrome associated with high fatality rates. Hantavirus particles are lipid-enveloped and display a characteristic surface lattice built up of tetragonal spikes composed of two glycoproteins, Gn and Gc. The pleomorphism of these particles has hindered cryo-EM efforts to obtain detailed structural information and only by using a combination of X-ray crystallography and cryo-electron tomography it was possible to build an atomic model of the surface lattice. Here we review these structural efforts and the unanticipated evolutionary relations between hantaviruses and alphaviruses highlighted by these studies.
Topics: Glycoproteins; Orthohantavirus; Hantavirus Infections; Humans; Membrane Glycoproteins; RNA Viruses
PubMed: 34418649
DOI: 10.1016/j.coviro.2021.07.009