Contemporary view about the pathogenesis  of Hantavirus nephropathy (Literature rewiew)

Hantavirus nephropathy (CVI) is considered to be acute kidney injury (AKI) associated with hantavirus infection (CVI). This infection in the countries of the European and Asian continents causes hemorrhagic fever with renal syndrome (HFRS). However, up to 60% of kidney damage is manifested by pathological changes in urinary sediment without signs of AKI, in connection with which the problems of terminology and diagnosis of kidney damage in HFRS were discussed. A review of the world literature of recent years, devoted to the study of modern data on the pathogenesis of CVI, is presented. The data were revealed that explain the organ specificity of the pathological process in different variants of CVI. The data were revealed that explain the organ specificity of the pathological process in different variants of CVI. The mechanisms related to various aspects of the pathogenesis of hantavirus nephropathy are considered. The factors that alter the functional activity of target cells through the direct action of the virus and the factors mediated by the immune response of the biological host to viral proteins in the form of the action of cytokines ("cytokine storm") causing damage to target organs (indirect factors) are listed. The influence of the hantavirus serotype, genetic factors, and the nature of the immune response of the biological host organism on the severity of renal dysfunction was shown. The concept of "acute damage to podocytes" is disclosed, which explains massive protein uria at the onset of the disease. The molecular and cellular mechanisms of damage to the main compartments of the kidney during hantavirus infection are presented. Disorders of hemostasis and mechanisms of hypercoagulation were demonstrated that underlie glomerular AKI due to acute microvascular syndrome, which is realized in the form of disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), and thrombotic microangiopathy (TMA). The results of experimental data obtained on a laboratory model of infection and in cell culture, histological studies of autopsy material, and nephrobiopsy specimens from patients with hantavirus nephropathy are demonstrated.

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Clinical and morphological parallels of lung and kidney damage in COVID-19

Nephrology (Saint-Petersburg) ◽

10.36485/1561-6274-2020-24-5-97-107 ◽

2020 ◽

Vol 24 (5) ◽

pp. 97-107

Author(s):

A. S. Litvinov ◽

A. V. Savin ◽

A. A. Kukhtina ◽

D. A. Sitovskaya

Keyword(s):

Morphological Changes ◽

Human Kidney ◽

Pathological Process ◽

Kidney Damage ◽

Viral Reservoir ◽

Target Cells ◽

Acute Renal Injury ◽

Target Organs ◽

Autopsy Data ◽

Lung And Kidney

This article reviews the available literature on the SARS-Cov-2 virus and its similarities with its predecessors. The mechanisms of infection due to the structure and epidemiology of the virus are described. Based on these data, the pathogenesis of COVID- 19 infection is described. Based on this, the authors suggest probable extrapulmonary target cells and target organs for the virus depending on their expression ofthe vector protein, APF-2. The article describes a classic clinical picture of the disease, possible complications of its course, and the extrapulmonary (cardiac, immunological, renal) manifestations ofthe infection. The authors traced and described the chain of knowledge about the involvement of the kidneys in the pathological process at COVID-19. Based on numerous studies, we are looking at the site of acute renal injury, coagulopathy, systemic inflammatory response in the spectrum of manifestations of COVID-19 relative to kidneys in patients with COVID-19, including those with hemodialysis. The article builds clinical-morphological associations between lung and kidney damage at COVID-19. We present new data on the pathomorphological manifestations of COVID-19 in the lungs, including own autopsy data. Specificsigns of the effects of the virus on alveolocytes and its cytopathic effect are highlighted and described. The article focuses on kidney signs of infection. The authors give new results of their own observations obtained during an autopsy of patients with COVID-19. Detailed morphological changes in kidney structures have been described, proving that the human kidney is a specific target for SARS-Cov-2 infection, and can also serve as a viral reservoir for the pathogen, playing a role in its subsequent persistence.

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Hantavirus Causing Hemorrhagic Fever with Renal Syndrome Enters from the Apical Surface and Requires Decay-Accelerating Factor (DAF/CD55)

Journal of Virology ◽

10.1128/jvi.02210-07 ◽

2008 ◽

Vol 82 (9) ◽

pp. 4257-4264 ◽

Cited By ~ 79

Author(s):

Ellen Krautkrämer ◽

Martin Zeier

Keyword(s):

Endothelial Cells ◽

Epithelial Cells ◽

Cell Surface ◽

Hemorrhagic Fever ◽

Hantavirus Infection ◽

Target Cells ◽

Apical Surface ◽

Decay Accelerating Factor ◽

African Green Monkey Kidney ◽

Old World

ABSTRACT The Old World hantaviruses, members of the family Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS). Transmission to humans occurs via inhalation of aerosols contaminated with the excreta of infected rodents. The viral antigen is detectable in dendritic cells, macrophages, lymphocytes, and, most importantly, microvascular endothelial cells. However, the site and detailed mechanism of entry of HFRS-causing hantaviruses in polarized epithelial cells have not yet been defined. Therefore, this study focused on the entry of the pathogenic hantaviruses Hantaan and Puumala into African green monkey kidney epithelial cells and primary human endothelial cells. The polarized epithelial and endothelial cells were found to be susceptible to hantavirus infection exclusively from the apical surface. Treatment with phosphatidylinositol-specific phospholipase C, which removes glycosylphosphatidylinositol (GPI)-anchored proteins from the cell surface, protects cells from infection, indicating that hantaviruses require a GPI-anchored protein as a cofactor for entry. Decay-accelerating factor (DAF)/CD55 is a GPI-anchored protein of the complement regulatory system and serves as a receptor for attachment to the apical cell surface for a number of viruses. Infection was reduced by the pretreatment of hantaviral particles with human recombinant DAF. Moreover, the treatment of permissive cells with DAF-specific antibody blocked infection. These results demonstrate that the Old World hantaviruses Hantaan and Puumala enter polarized target cells from the apical site and that DAF is a critical cofactor for infection.

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Bioinformatics Analysis of Allele Frequencies and Expression Patterns of ACE2, TMPRSS2 and FURIN in Different Populations and Susceptibility to SARS-CoV-2

Genes ◽

10.3390/genes12071041 ◽

2021 ◽

Vol 12 (7) ◽

pp. 1041

Author(s):

Mohammad Tarek ◽

Hana Abdelzaher ◽

Firas Kobeissy ◽

Hassan A. N. El-Fawal ◽

Mohammed M. Salama ◽

...

Keyword(s):

Immune Response ◽

Genetic Factors ◽

Bioinformatics Analysis ◽

Expression Patterns ◽

Spike Protein ◽

Target Cells ◽

Health Crisis ◽

Expression Levels ◽

Different Populations ◽

Shed Light

The virus responsible for the COVID-19 global health crisis, SARS-CoV-2, has been shown to utilize the ACE2 protein as an entry point to its target cells. The virus has been shown to rely on the actions of TMPRSS2 (a serine protease), as well as FURIN (a peptidase), for the critical priming of its spike protein. It has been postulated that variations in the sequence and expression of SARS-CoV-2’s receptor (ACE2) and the two priming proteases (TMPRSS2 and FURIN) may be critical in contributing to SARS-CoV-2 infectivity. This study aims to examine the different expression levels of FURIN in various tissues and age ranges in light of ACE2 and TMPRSS2 expression levels using the LungMAP database. Furthermore, we retrieved expression quantitative trait loci (eQTLs) of the three genes and their annotation. We analyzed the frequency of the retrieved variants in data from various populations and compared it to the Egyptian population. We highlight FURIN’s potential interplay with the immune response to SARS-CoV-2 and showcase a myriad of variants of the three genes that are differentially expressed across populations. Our findings provide insights into potential genetic factors that impact SARS-CoV-2 infectivity in different populations and shed light on the varying expression patterns of FURIN.

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Stability and Hopf bifurcation analysis of immune response delayed HIV type 1 infection model with two target cells

Mathematical Methods in the Applied Sciences ◽

10.1002/mma.3306 ◽

2014 ◽

Vol 38 (17) ◽

pp. 3653-3669 ◽

Cited By ~ 1

Author(s):

P. Balasubramaniam ◽

M. Prakash ◽

P. Tamilalagan

Keyword(s):

Immune Response ◽

Hopf Bifurcation ◽

Bifurcation Analysis ◽

Infection Model ◽

Target Cells ◽

Hiv Type 1

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Pathogen Dose in Animal Models of Hemorrhagic Fever Virus Infections and the Potential Impact on Studies of the Immune Response

Pathogens ◽

10.3390/pathogens10030275 ◽

2021 ◽

Vol 10 (3) ◽

pp. 275

Author(s):

Bryce M. Warner

Keyword(s):

Immune Response ◽

Animal Models ◽

Hemorrhagic Fever ◽

Virus Infections ◽

Critical Determinant ◽

Animal Models Of Disease ◽

Hemorrhagic Fever Virus ◽

Immune Correlates ◽

Clinical Drug Development ◽

Wide Range

Viral hemorrhagic fever viruses come from a wide range of virus families and are a significant cause of morbidity and mortality worldwide each year. Animal models of infection with a number of these viruses have contributed to our knowledge of their pathogenesis and have been crucial for the development of therapeutics and vaccines that have been approved for human use. Most of these models use artificially high doses of virus, ensuring lethality in pre-clinical drug development studies. However, this can have a significant effect on the immune response generated. Here I discuss how the dose of antigen or pathogen is a critical determinant of immune responses and suggest that the current study of viruses in animal models should take this into account when developing and studying animal models of disease. This can have implications for determination of immune correlates of protection against disease as well as informing relevant vaccination and therapeutic strategies.

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MO426HANTA HEMORRHAGIC FEVER WITH RENAL SYNDROME CAUSED BY HANTAAN SEROTIPE IN BALKAN PENINSULA - AN UNESPECTED FINDING

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab083.0018 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Gabriela Elena Lupusoru ◽

Ioana-Georgiana Ailincai ◽

Andreea Gabriella Andronesi ◽

Mircea Lupusoru ◽

Lavinia Maria Bernea ◽

...

Keyword(s):

Kidney Biopsy ◽

Hemorrhagic Fever ◽

Balkan Peninsula ◽

Secondary Hypertension ◽

Blue Staining ◽

Hantavirus Infection ◽

Severe Thrombocytopenia ◽

Toluidine Blue Staining ◽

Foot Process ◽

Hepatic Cytolysis

Abstract Background and Aims Hantavirus infection is a zoonosis rare in the Balkan Peninsula but with increasing frequency and geographic spread, causing two major syndromes, depending on the viral serotype: hemorrhagic fever with renal syndrome (HFRS) and cardiopulmonary syndrome (CPS). Because there is no specific treatment or vaccine for this condition, the key for minimizing the progression to chronic kidney disease, secondary hypertension or death is early diagnosis and prompt therapy. This paper presents a case of HFSR in which needle kidney biopsy played a major role in diagnosis and draws attention on this zoonosis that might be highly underdiagnosed in Balkan Peninsula. Method A 26-year-old female with no medical history was admitted in our department with acute kidney injury (AKI), nephritic syndrome with nephrotic range proteinuria, high blood pressure, hepatic cytolysis, severe thrombocytopenia, anemia and leukocytosis, elevated LDH, normal haptoglobin, positive Coombs test (Table 1). Immunological testing (C3, C4, ANA, ANCA, antiGBM), viral infection markers (hepatitis B/C, HIV, Epstein-Barr, Cytomegalovirus), IgA/M/G were all negative and ADAMTS13 activity was normal. Abdominal sonography showed both kidneys of normal size and shape. A kidney biopsy was performed. The biopsy specimen showed macroscopic features of hemorrhage in the renal medulla. In immunofluorescence the staining was negative for IgA, IgG, IgM, C1q, C3c, k and λ chains, albumin and fibrinogen. Light microscopy (LM) revealed normal glomeruli and arterioles, dilated proximal tubules with resorption droplets at the apical pole and erythrocytes in the lumen, important interstitial hemorrhage in the medulla, with no inflammation or interstitial fibrosis. The electron microscopy (EM) showed segmental foot process effacement, endotheliosis of the peritubular capillaries, rare plasmocytes and macrophages in the interstitium (Figure 1). The aspect of hemorrhagic interstitial nephritis suggested Hantavirus infection. Serological testing revealed both IgM and IgG antibodies for the Hantaan serotype (HTNV). The final diagnosis was HTNV hemorrhagic interstitial nephritis with intrinsic AKI and secondary hypertension. MO426 Figure 1: A, B LM, Toluidine Blue staining. Normal glomerulus. Resorption droplets in the proximal tubular cells. C, D LM, Toluidine Blue staining. Extensive interstitial hemorrhage in medulla, tubulitis. E EM. Interstitial extravasation of erythrocytes. F EM. Endothelial swelling, foot process effacement. Results The patient was treated with oral methylprednisolone 16mg/d for 2 weeks, with progressive tampering of the dose and removal after 2 months. She received antihypertensive and antiproteinuric treatment with ramipril. The evolution was good, with creatinine and liver enzymes returning to normal. Conclusion HFRS belongs to a group of rare zoonoses in Balkan Peninsula, the most involved serotypes being Dobrava and Puumala. This case had positive serology for HTNV usually being found in China and Russia, but our patient didn’t travel abroad before she got ill, so we can’t consider the case as being an imported infection. That highlights a possible underdiagnosis of the disease in this region and also the need to re-evaluate geographic distribution of different strains and changes in ecological aspects given that they may pose a major risk to public health. The disease begins with flu-like symptoms and progresses to AKI with severe thrombocytopenia, anemia and coagulation disorders, being easily mistaken for haemolytic uremic syndrome. In a region with sporadic cases, we face diagnosis difficulties related especially to the absence of initial diagnosis suspicion, so we emphasize the need to include this pathology in the differential diagnosis algorithm of diseases evolving with thrombocytopenia, anemia, hepatic cytolysis and renal injury.

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Anterior pituitary lobe atrophy as late complication of hemorrhagic fever with renal syndrome

Vojnosanitetski pregled ◽

10.2298/vsp0902166j ◽

2009 ◽

Vol 66 (2) ◽

pp. 166-168

Author(s):

Dragan Jovanovic ◽

Zoran Kovacevic ◽

Tamara Dragovic ◽

Marijana Petrovic ◽

Jelena Tadic

Keyword(s):

Renal Insufficiency ◽

Anterior Pituitary ◽

Late Complication ◽

Sella Turcica ◽

Hemorrhagic Fever ◽

Empty Sella ◽

Acute Stage ◽

Hantavirus Infection ◽

Multisystemic Disease ◽

Acute Renal Insufficiency

Introduction. Hemorrhagic fever with renal syndrome (HFRS) is acute infective multisystemic disease followed by febrility, hemorrhages and acute renal insufficiency. Bleeding in the anterior pituitary lobe leading to tissue necrosis occurs in acute stage of severe clinical forms of HFRS, while atrophy of the anterior pituitary lobe with diminution of the gland function occurs after recovery stage. Case report. We presented a patient with the development of chronic renal insufficiency and hypopituitarism as complication that had been diagnosed six years after Hantavirus infection. Magnetic resonance of the pituitary gland revealed atrophy and empty sella turcica. Conclusion. Regarding frequency of this viral infection and its endemic character in some parts of our country partial and/or complete loss of pituitary function should be considered during the late stage of HFRS.

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Mastitis in Small Ruminants

10.5772/intechopen.97585 ◽

2021 ◽

Author(s):

Christine T. Mwenge Kahinda

Keyword(s):

Immune Response ◽

Complex Disease ◽

Antimicrobial Agents ◽

Defense Mechanism ◽

Human Health Risk ◽

Small Ruminants ◽

Economic Loss ◽

Pathological Process ◽

Response Mechanism ◽

Immunological Responses

Bacterial mastitis in small ruminants is a complex disease, with massive economic loss in dairy sheep/goat industry due to poor productivity. The current mastitis prevention strategy relies on culling of infected ewes or does and or the use of antimicrobial agents to eliminate the bacterial infection. This has a potential risk for developing antibiotic resistant bacteria, posing human health risk from consumption of raw sheep or goat dairy products. Existing experimental and licensed vaccines on the market are ineffective against reducing the risk of mastitis in herds or flocks. Raising the needs for development of improved vaccines against mastitis for use in sheep and goats. This review examines, current understanding of the pathological processes and immunological responses against bacterial mastitis, using S. aureus as an example. By highlighting the protective defense mechanism induced in the udder against S. aureus mastitis. Based on evidence from published studies on pathological process and protective immune response mechanism, the need for improved vaccines for prevention of mastitis in small ruminant is highlighted and the development of a vaccine capable of enhancing immune response mechanism, that reduce the establishment of intramammary infection through induction of local IgA, IgG2 and Th17 immune responses is proposed.

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Hemorrhagic fever with renal syndrome with concurrent aortic dissection: a case report

10.21203/rs.3.rs-49633/v1 ◽

2020 ◽

Author(s):

Fengqi Qiu ◽

Congcong Li ◽

Jianya Zhou

Keyword(s):

Acute Kidney Injury ◽

Aortic Dissection ◽

Kidney Injury ◽

Hemorrhagic Fever ◽

Sudden Onset ◽

High Fever ◽

Hantaan Virus ◽

Hantavirus Infection ◽

Microvascular Damage ◽

Stanford B

Abstract Background Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses presenting with high fever, hemorrhage, acute kidney injury. Microvascular injury and hemorrhage in mucus was often observed in patients with hantavirus infection. Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically. We present a previously unreported case of hemorrhagic fever with concurrent Stanford B aortic dissection. Case presentation: A 56-year-old man complained of high fever, generalized body ache, with decreased platelet counts of 10 × 10^9/L and acute kidney injury. The ELISA test for Hantaan virus of IgM and IgG antibodies were both positive. During the convalescent period, he complained sudden onset acute chest pain radiating to the back and the CTA revealed an aortic dissection of the descending aorta extending to iliac artery. He was diagnosed with Hemorrhagic fever with renal syndrome and Stanford B aortic dissection. The patient recovered completely after surgery with other support treatments. Conclusion We present a case of HFRS complicated with aortic dissection,and no study has reported the association of HFRS with aortic disease. However, we suppose that hantavirus infection not only cause microvascular damage but may be risk factor for acute macrovascular detriment. A causal relationship has yet to be confirmed.

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