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Viruses Mar 2014Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever... (Review)
Review
Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships.
Topics: Animals; Asymptomatic Diseases; Carrier State; Disease Reservoirs; Orthohantavirus; Hantavirus Infections; Host-Pathogen Interactions; Rodentia
PubMed: 24638205
DOI: 10.3390/v6031317 -
Viruses Feb 2022Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. Characteristic clinical findings include acute kidney injury (AKI), thrombocytopenia, and...
Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. Characteristic clinical findings include acute kidney injury (AKI), thrombocytopenia, and capillary leakage. Smoking increases the risk of severe AKI, but it is not known whether alcohol consumption predisposes patients to a more severe infection. Liver and pancreatic enzymes, as well as biomarkers of alcohol consumption (gamma-glutamyl transferase, GGT; carbohydrate-deficient transferrin, CDT; GGT-CDT combination; and ethyl glucuronide, EtG), were measured from 66 patients with acute PUUV infection during hospitalization and at the convalescence phase. Alcohol consumption was present in 41% of the study population, 15% showing signs of heavy drinking. Alcohol use did not affect the severity of PUUV induced AKI nor the overall clinical picture of the infection. Liver enzyme levels (GGT or alanine aminotransferase, ALT) were elevated in 64% of the patients, but the levels did not associate with the markers reflecting the severity of the disease. Serum amylase activities at the convalescent stage were higher than those at the acute phase (p < 0.001). No cases with acute pancreatitis were found. In conclusion, our findings indicate that alcohol consumption does not seem to affect the clinical course of an acute PUUV infection.
Topics: Acute Disease; Acute Kidney Injury; Alcohol Drinking; Biomarkers; Orthohantavirus; Hantavirus Infections; Hemorrhagic Fever with Renal Syndrome; Humans; Pancreatitis; Puumala virus
PubMed: 35336910
DOI: 10.3390/v14030500 -
Antiviral Research Apr 2020The 2019 11th International Conference on Hantaviruses (ICH 2019) was organized by the International Society for Hantaviruses (ISH), and held on September 1-4, 2019, at... (Review)
Review
The 2019 11th International Conference on Hantaviruses (ICH 2019) was organized by the International Society for Hantaviruses (ISH), and held on September 1-4, 2019, at the Irish College, in Leuven, Belgium. These ICHs have been held every three years since 1989. ICH 2019 was attended by 158 participants from 33 countries. The current report summarizes research presented on all aspects of hantavirology: ecology; pathogenesis and immune responses; virus phylogeny, replication and morphogenesis; epidemiology; vaccines, therapeutics and prevention; and clinical aspects and diagnosis.
Topics: Belgium; Congresses as Topic; Orthohantavirus; Hantavirus Infections; Humans; Research
PubMed: 32068071
DOI: 10.1016/j.antiviral.2020.104733 -
Thrombosis Research Jan 2024Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is...
Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation. Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro, but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration. Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target.
Topics: Humans; Puumala virus; Hemorrhagic Fever with Renal Syndrome; Endothelial Cells; Orthohantavirus; Thrombocytopenia
PubMed: 38006765
DOI: 10.1016/j.thromres.2023.11.017 -
PLoS Neglected Tropical Diseases Aug 2019Several viruses from the genus Orthohantavirus are known to cause lethal disease in humans. Sigmodontinae rodents are the main hosts responsible for hantavirus...
Several viruses from the genus Orthohantavirus are known to cause lethal disease in humans. Sigmodontinae rodents are the main hosts responsible for hantavirus transmission in the tropical forests, savannas, and wetlands of South America. These rodents can shed different hantaviruses, such as the lethal and emerging Araraquara orthohantavirus. Factors that drive variation in host populations may influence hantavirus transmission dynamics within and between populations. Landscape structure, and particularly areas with a predominance of agricultural land and forest remnants, is expected to influence the proportion of hantavirus rodent hosts in the Atlantic Forest rodent community. Here, we tested this using 283 Atlantic Forest rodent capture records and geographically weighted models that allow us to test if predictors vary spatially. We also assessed the correspondence between proportions of hantavirus hosts in rodent communities and a human vulnerability to hantavirus infection index across the entire Atlantic Forest biome. We found that hantavirus host proportions were more positively influenced by landscape diversity than by a particular habitat or agricultural matrix type. Local small mammal diversity also positively influenced known pathogenic hantavirus host proportions, indicating that a plasticity to habitat quality may be more important for these hosts than competition with native forest dwelling species. We found a consistent positive effect of sugarcane and tree plantation on the proportion of rodent hosts, whereas defaunation intensity did not correlate with the proportion of hosts of potentially pathogenic hantavirus genotypes in the community, indicating that non-defaunated areas can also be hotspots for hantavirus disease outbreaks. The spatial match between host hotspots and human disease vulnerability was 17%, while coldspots matched 20%. Overall, we discovered strong spatial and land use change influences on hantavirus hosts at the landscape level across the Atlantic Forest. Our findings suggest disease surveillance must be reinforced in the southern and southeastern regions of the biome where the highest predicted hantavirus host proportion and levels of vulnerability spatially match. Importantly, our analyses suggest there may be more complex rodent community dynamics and interactions with human disease than currently hypothesized.
Topics: Agriculture; Animals; Biodiversity; Disease Reservoirs; Disease Transmission, Infectious; Ecosystem; Forests; Orthohantavirus; Hantavirus Infections; Humans; Rodentia; South America; Spatial Analysis
PubMed: 31404077
DOI: 10.1371/journal.pntd.0007655 -
Kidney International Jan 2013The function of the kidney with its highly differentiated and specialized cell types is affected by infection with several viruses. Viral infections of the kidney have a... (Review)
Review
The function of the kidney with its highly differentiated and specialized cell types is affected by infection with several viruses. Viral infections of the kidney have a negative impact not only on patients undergoing renal transplantation and immunosuppression. Besides the increasing number of patients suffering from HIV-associated nephropathy, another group of viruses infects immunocompetent patients and induces renal failure. Hantaviruses belong nowadays to the emerging zoonoses that increase in number and geographic distribution. The viruses are distributed worldwide in endemic areas and distribution seems to expand. Together with the increase in the number of cases in the last few years, the understanding of epidemiology and pathology has deepened and some concepts had to be changed. Symptoms and mortality vary between species. The classification refers to geographical distribution: New World hantaviruses causing hantavirus cardiopulmonary syndrome (HCPS) and Old World hantaviruses causing hemorrhagic fever with renal syndrome (HFRS). Indeed, in most HFRS cases, the kidney is mainly affected and HCPS is characterized by cardiopulmonary involvement. But the picture of strict organ tropism is changing and reports of pulmonary findings and nonrenal manifestations in infections with Old World hantaviruses are increasing. However, the overall symptoms-vascular alterations and leakage-that are responsible for organ failure are characteristic for all diseases caused by hantaviruses.
Topics: Acute Kidney Injury; Antiviral Agents; Orthohantavirus; Hantavirus Infections; Humans; Kidney; Prevalence
PubMed: 23151954
DOI: 10.1038/ki.2012.360 -
Journal of Molecular Biology Mar 2022The genus Orthohantavirus (family Hantaviridae, order Bunyavirales) consists of numerous genetic and pathologically distinct viral species found within rodent and... (Review)
Review
The genus Orthohantavirus (family Hantaviridae, order Bunyavirales) consists of numerous genetic and pathologically distinct viral species found within rodent and mammalian insectivore populations world-wide. Although reservoir hosts experience persistent asymptomatic infection, numerous rodent-borne orthohantaviruses cause severe disease when transmitted to humans, with case-fatality rates up to 40%. The first isolation of an orthohantavirus occurred in 1976 and, since then, the field has made significant progress in understanding the immune correlates of disease, viral interactions with the human innate immune response, and the immune kinetics of reservoir hosts. Much still remains elusive regarding the molecular mechanisms of orthohantavirus recognition by the innate immune response and viral antagonism within the reservoir host, however. This review provides a summary of the last 45 years of research into orthohantavirus interaction with the host innate immune response. This summary includes discussion of current knowledge involving human, non-reservoir rodent, and reservoir innate immune responses to viruses which cause hemorrhagic fever with renal syndrome and hantavirus cardio-pulmonary syndrome. Review of the literature concludes with a brief proposition for the development of novel tools needed to drive forward investigations into the molecular mechanisms of innate immune activation and consequences for disease outcomes in the various hosts for orthohantaviruses.
Topics: Animals; Orthohantavirus; Hantavirus Infections; Humans; Immunity, Innate
PubMed: 34487792
DOI: 10.1016/j.jmb.2021.167230 -
Human Vaccines Jun 2011Hantaviruses are emerging viruses which are hosted by small mammals. When transmitted to humans, they can cause two clinical syndromes, hemorrhagic fever with renal... (Review)
Review
Hantaviruses are emerging viruses which are hosted by small mammals. When transmitted to humans, they can cause two clinical syndromes, hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. The review compiles the current list of hantaviruses which are thought to be pathogenic in humans on the basis of molecular or at least serological evidence. Whereas induction of a neutralizing humoral immune response is considered to be protective against infection, the dual role of cellular immunity (protection versus immunopathogenicity) is discussed. For active immunisation, inactivated virus vaccines are licensed in certain Asian countries. Moreover, several classical and molecular vaccine approaches are in pre-clinical stages of development. The development of hantavirus vaccines is hampered by the lack of adequate animal models of hantavirus-associated disease. In addition to active immunization strategies, the review summarizes other ways of infection prevention, as passive immunization, chemoprophylaxis, and exposition prophylaxis.
Topics: Adaptive Immunity; Orthohantavirus; Hantavirus Infections; Humans; Vaccination; Vaccines, Synthetic; Viral Vaccines
PubMed: 21508676
DOI: 10.4161/hv.7.6.15197 -
Emerging Infectious Diseases Jan 2018We captured 3 hantavirus rodent hosts in Otamendi Natural Reserve, Argentina, during 2007-2012. Hantavirus antibodies were found only in Akodon azarae grass mice, mainly...
We captured 3 hantavirus rodent hosts in Otamendi Natural Reserve, Argentina, during 2007-2012. Hantavirus antibodies were found only in Akodon azarae grass mice, mainly in males and old animals. Higher abundance of this species was associated with warm and rainy weather and high water levels, which peaked after a strong El Niño event.
Topics: Animals; Antibodies, Viral; Argentina; Communicable Diseases, Emerging; Disease Reservoirs; Ecosystem; Orthohantavirus; Hantavirus Infections; Population Density; Rodent Diseases; Rodentia; Time Factors; Zoonoses
PubMed: 29260665
DOI: 10.3201/eid2401.171372 -
The Journal of General Virology Oct 2020Type I interferon receptor knockout mice (strain A129) were assessed as a disease model of hantavirus infection. A range of infection routes (intramuscular,...
Type I interferon receptor knockout mice (strain A129) were assessed as a disease model of hantavirus infection. A range of infection routes (intramuscular, intraperitoneal and intranasal) were assessed using minimally passaged Seoul virus (strain Humber). Dissemination of virus to the spleen, kidney and lung was observed at 5 days after intramuscular and intraperitoneal challenge, which was resolved by day 14. In contrast, intranasal challenge of A129 mice demonstrated virus tropism to the lung, which was maintained to day 14 post-challenge. These data support the use of the A129 mouse model for future infection studies and the evaluation of interventions.
Topics: Animals; Disease Models, Animal; Orthohantavirus; Hantavirus Infections; Hemorrhagic Fever with Renal Syndrome; Kidney; Liver; Lung; Male; Mice; Mice, Knockout; RNA, Viral; Receptor, Interferon alpha-beta; Spleen; Viral Tropism
PubMed: 32667279
DOI: 10.1099/jgv.0.001470