Uncovering the mysteries of hantavirus infections
TL;DR: The basic molecular properties and cell biology of hantaviruses are discussed and an overview of virus-induced pathology, in particular vascular leakage and immunopathology is offered.
Abstract: Hantaviruses are negative-sense single-stranded RNA viruses that infect many species of rodents, shrews, moles and bats. Infection in these reservoir hosts is almost asymptomatic, but some rodent-borne hantaviruses also infect humans, causing either haemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS). In this Review, we discuss the basic molecular properties and cell biology of hantaviruses and offer an overview of virus-induced pathology, in particular vascular leakage and immunopathology.
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TL;DR: The features of atherosclerosis as an inflammatory vascular disease highlighting the role of platelet crosstalk with cellular and soluble factors involved in atheroprogression and translational implications of platelets' interaction with other immune cells are discussed.
Abstract: Platelets contribute to processes beyond thrombus formation and may play a so far underestimated role as an immune cell in various circumstances. This review outlines immune functions of platelets in host defense, but also how they may contribute to mechanisms of infectious diseases. A particular emphasis is placed on the interaction of platelets with other immune cells. Furthermore, this article outlines the features of atherosclerosis as an inflammatory vascular disease highlighting the role of platelet crosstalk with cellular and soluble factors involved in atheroprogression. Understanding, how platelets influence these processes of vascular remodeling will shed light on their role for tissue homeostasis beyond intravascular thrombosis. Finally, translational implications of platelet-mediated inflammation in atherosclerosis are discussed.
450 citations
Cites background from "Uncovering the mysteries of hantavi..."
...Furthermore, platelets play an important role in infections by Leishmania (60) and in the pathogenesis of Hantavirus infection (61)....
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TL;DR: Several distinct phenotypes associated with increased host resistance to malaria are overrepresented in populations living in areas where malaria is endemic, as a result of evolutionary pressures.
Abstract: SUMMARY Blood group antigens represent polymorphic traits inherited among individuals and populations. At present, there are 34 recognized human blood groups and hundreds of individual blood group antigens and alleles. Differences in blood group antigen expression can increase or decrease host susceptibility to many infections. Blood groups can play a direct role in infection by serving as receptors and/or coreceptors for microorganisms, parasites, and viruses. In addition, many blood group antigens facilitate intracellular uptake, signal transduction, or adhesion through the organization of membrane microdomains. Several blood groups can modify the innate immune response to infection. Several distinct phenotypes associated with increased host resistance to malaria are overrepresented in populations living in areas where malaria is endemic, as a result of evolutionary pressures. Microorganisms can also stimulate antibodies against blood group antigens, including ABO, T, and Kell. Finally, there is a symbiotic relationship between blood group expression and maturation of the gastrointestinal microbiome.
386 citations
Cites background from "Uncovering the mysteries of hantavi..."
...3 integrins, C1q, and CD55 have been shown to bind hantaviruses in vitro (640)....
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...Hantavirus is zoonotic illness spread by mice and other rodents (640)....
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TL;DR: The recent genetic and structural advances that have revealed important insights into the composition of orthobunyavirus virions, viral transcription and replication and viral interactions with the host innate immune response are described.
Abstract: Orthobunyaviruses are transmitted by arthropod vectors and can infect humans, animals and crops. In this Review, Elliott describes recent genetic and structural advances that have revealed important insights into the composition of orthobunyavirus virions, viral transcription and replication, and viral interactions with the host innate immune response.
185 citations
TL;DR: The current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors are reviewed and the treatment and prevention will be discussed.
Abstract: Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China. The reservoir host of HTNV is field mouse (Apodemus agraricus). The main manifestation of HFRS, including acute kidney injury, increases vascular permeability, and coagulation abnormalities. In this paper, we review the current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors. Furthermore, the treatment and prevention will be discussed.
167 citations
Cites background from "Uncovering the mysteries of hantavi..."
...Vaheri et al. (2013) found that these molecules were produced by various cells, such as macrophages, monocytes, and lymphocytes, in response to pro-inflammatory signals and participate in the regulation of inflammation....
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...In humans, the clinical procedure of hantavirus infections is affected by host genes (Vaheri et al., 2013)....
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TL;DR: It is determined that both ANG1 and ANG2 binding to Tie2 increases Tie1-Tie2 interactions in a β1 integrin-dependent manner and that Tie1 regulates ANG-induced Tie2 trafficking in endothelial cells, which supports a model in which Tie1 directly interacts with Tie2 to promote ANG- induced vascular responses under noninflammatory conditions.
Abstract: The angiopoietin/Tie (ANG/Tie) receptor system controls developmental and tumor angiogenesis, inflammatory vascular remodeling, and vessel leakage. ANG1 is a Tie2 agonist that promotes vascular stabilization in inflammation and sepsis, whereas ANG2 is a context-dependent Tie2 agonist or antagonist. A limited understanding of ANG signaling mechanisms and the orphan receptor Tie1 has hindered development of ANG/Tie-targeted therapeutics. Here, we determined that both ANG1 and ANG2 binding to Tie2 increases Tie1-Tie2 interactions in a β1 integrin-dependent manner and that Tie1 regulates ANG-induced Tie2 trafficking in endothelial cells. Endothelial Tie1 was essential for the agonist activity of ANG1 and autocrine ANG2. Deletion of endothelial Tie1 in mice reduced Tie2 phosphorylation and downstream Akt activation, increased FOXO1 nuclear localization and transcriptional activation, and prevented ANG1- and ANG2-induced capillary-to-venous remodeling. However, in acute endotoxemia, the Tie1 ectodomain that is responsible for interaction with Tie2 was rapidly cleaved, ANG1 agonist activity was decreased, and autocrine ANG2 agonist activity was lost, which led to suppression of Tie2 signaling. Tie1 cleavage also occurred in patients with hantavirus infection. These results support a model in which Tie1 directly interacts with Tie2 to promote ANG-induced vascular responses under noninflammatory conditions, whereas in inflammation, Tie1 cleavage contributes to loss of ANG2 agonist activity and vascular stability.
162 citations
Cites background from "Uncovering the mysteries of hantavi..."
...To determine whether Tie1 cleavage occurred in human inflammatory disease, we then measured soluble Tie1 ectodomain (sTie1) in the serum of patients with acute Puumala hantavirus (PUUV) disease (58)....
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References
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TL;DR: This review summarizes key recent developments and proposes a unifying model for the role of IDO in tolerance induction, including studies of mammalian pregnancy, tumour resistance, chronic infections and autoimmune diseases.
Abstract: Indoleamine 2,3-dioxygenase (IDO) is an enzyme that degrades the essential amino acid tryptophan. The concept that cells expressing IDO can suppress T-cell responses and promote tolerance is a relatively new paradigm in immunology. Considerable evidence now supports this hypothesis, including studies of mammalian pregnancy, tumour resistance, chronic infections and autoimmune diseases. In this review, we summarize key recent developments and propose a unifying model for the role of IDO in tolerance induction.
2,184 citations
TL;DR: With IL 6 transgenic mice, deregulation of the IL 6 expression was suggested to be involved in the generation of plasmacytoma/myeloma and mesangium proliferative glomerulonephritis and the findings suggest the presence of a positive regulatory loop in acute‐phase reaction.
Abstract: Interleukin 1 (IL 1), IL 6, and tumor necrosis factor (TNF) are typical examples of multifunctional cytokines involved in the regulation of the immune response, hematopoiesis, and inflammation. Their functions are widely overlapping but each shows its own characteristic properties. IL 6 was originally identified as a B cell differentiation factor, and thus one of the major functions of IL 6 is antibody induction. Transgenic mice have provided much needed information on the pathophysiological role of cytokines. With IL 6 transgenic mice, deregulation of the IL 6 expression was suggested to be involved in the generation of plasmacytoma/myeloma and mesangium proliferative glomerulonephritis. The cis-regulatory elements and trans-acting nuclear factor (or factors) for the IL 6 expression (NF-IL 6) have been identified. NF-IL 6 was shown to be a member of a C/EBP family, and the possible involvement of NF-IL 6 not only in the IL 6 regulation but also in the induction of various acute phase proteins was also ob...
1,290 citations
TL;DR: Current concepts regarding the ecology of and disease associated with these serious human pathogens are presented and an integration of the ecology and evolution of these and other host-virus ecosystems through modeling and hypothesis-driven research with the risk of emergence, host switching/spillover, and disease transmission to humans.
Abstract: Summary: Hantaviruses are enzootic viruses that maintain persistent infections in their rodent hosts without apparent disease symptoms. The spillover of these viruses to humans can lead to one of two serious illnesses, hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and natural history of these viruses following an increase in the number of outbreaks in the Americas. In this review, current concepts regarding the ecology of and disease associated with these serious human pathogens are presented. Priorities for future research suggest an integration of the ecology and evolution of these and other host-virus ecosystems through modeling and hypothesis-driven research with the risk of emergence, host switching/spillover, and disease transmission to humans.
833 citations
TL;DR: Clinical, laboratory, and autopsy data on the first 17 persons with confirmed infection from this newly recognized strain of hantavirus identified as the cause of an outbreak of severe respiratory illness in the southwestern United States are analyzed.
Abstract: Background In May 1993 an outbreak of severe respiratory illness occurred in the southwestern United States. A previously unknown hantavirus was identified as the cause. In Asia hantaviruses are associated with hemorrhagic fever and renal disease. They have not been known as a cause of human disease in North America. Methods We analyzed clinical, laboratory, and autopsy data on the first 17 persons with confirmed infection from this newly recognized strain of hantavirus. Results The mean age of the patients was 32.2 years (range, 13 to 64); 61 percent were women, 72 percent were Native American, 22 percent white, and 6 percent Hispanic. The most common prodromal symptoms were fever and myalgia (100 percent), cough or dyspnea (76 percent), gastrointestinal symptoms (76 percent), and headache (71 percent). The most common physical findings were tachypnea (100 percent), tachycardia (94 percent), and hypotension (50 percent). The laboratory findings included leukocytosis (median peak cell count, 26,000 per cu...
568 citations
Journal Article•
TL;DR: Pulmonary histopathological features were similar in most of the fatal HPS cases and consisted of an interstitial pneumonitis with a variable mononuclear cell infiltrate, edema, and focal hyaline membranes, however, pulmonary features were significantly different and included diffuse alveolar damage and variable degrees of severe air space disorganization.
Abstract: A recent outbreak of a severe pulmonary disease in the southwestern United States was etiologically linked to a previously unrecognized hantavirus The virus has been isolated from its major reservoir, the deer mouse, Peromyscus maniculatus, and recently named Sin Nombre virus Clinically, the disease has become known as the hantavirus pulmonary syndrome (HPS) Since May 1993, 44 fatal cases of HPS have been identified through clinicopathological review and immunohistochemical (IHC) testing of tissues from 273 patients who died of an unexplained noncardiogenic pulmonary edema In 158 cases for which suitable specimens were available, serological testing and/or reverse transcription-polymerase chain reaction (RT-PCR) amplification of extracted RNA was also performed IHC, serological, and PCR results were concordant for virtually all HPS and non-HPS patients when more than one assay was performed The prodromal illness of HPS is similar to that of many other viral diseases Consistent hematological features include thrombocytopenia, hemoconcentration, neutrophilic leukocytosis with a left shift, and reactive lymphocytes Pulmonary histopathological features were similar in most of the fatal HPS cases (40/44) and consisted of an interstitial pneumonitis with a variable mononuclear cell infiltrate, edema, and focal hyaline membranes In four cases, however, pulmonary features were significantly different and included diffuse alveolar damage and variable degrees of severe air space disorganization IHC analysis showed widespread presence of hantaviral antigens in endothelial cells of the microvasculature, particularly in the lung Hantaviral antigens were also observed within follicular dendritic cells, macrophages, and lymphocytes Hantaviral inclusions were observed in endothelial cells of lungs by thinsection electron microscopy, and their identity was verified by immunogold labeling Virus-like particles were seen in pulmonary endothelial cells and macrophages HPS is a newly recognized, often fatal disease, with a spectrum of microscopic morphological changes, which may be an important cause of severe and fatal illness presenting as adult respiratory distress syndrome
568 citations