Hemorrhagic fever with renal syndrome: clinical, pathogenetic and therapeutic aspects

Павелкина, В. Ф.; Uskova, Yu.G.

doi:10.15507/0236-2910.027.201703.315-329

Cited by 4 publications

(4 citation statements)

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“…Phylogenetic analysis of PUUV identified in NE cases from the RT and the RM. The RT and the RM are part of the Volga Federal District, which is endemic for NE ( Figure 1 ) [ 3 , 4 , 5 , 6 ].…”

Section: Resultsmentioning

confidence: 99%

“…HFRS is typically characterized by fever, increased vascular permeability, thrombocytopenia, and acute kidney injury, and currently it has the highest incidence rate of all zoonotic virus infections reported in Russia [ 1 , 2 ]. Nephropathia Epidemica (NE) is a mild form of HFRS that is endemic in the Volga Federal District of Russia, that includes the Republic of Tatarstan (RT) and the Republic of Mordovia (RM) [ 3 , 4 , 5 , 6 ]. Mortality rate is low (0–0.4%) and complete recovery of kidney function without development of chronic renal disease or acute kidney injury (AKI) is commonly expected [ 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although NE is endemic in the RM [ 6 ], human immune responses to orthohantavirus infection remain largely un-characterized. In addition, details of the cytokine responses to hantavirus infection in patients with NE from the RM is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Cytokine, Chemokine, and Metalloprotease Activation in the Serum of Patients with Nephropathia Epidemica from the Republic of Tatarstan and the Republic of Mordovia, Russia

et al. 2021

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Nephropathia Epidemica (NE), endemic to several Volga regions of Russia, including the Republic of Tatarstan (RT) and the Republic of Mordovia (RM), is a mild form of hemorrhagic fever with renal syndrome caused by infection with rodent-borne orthohantaviruses. Although NE cases have been reported for decades, little is known about the hantavirus strains associated with human infection in these regions. There is also limited understanding of the pathogenesis of NE in the RT and the RM. To address these knowledge gaps, we conducted comparative analyses of patients with NE in the RT and the RM. Clinical symptoms were more severe in patients with NE from the RM with longer observed duration of fever symptoms and hospitalization. Analysis of patient sera showed changes in the levels of numerous cytokines, chemokines, and matrix metalloproteases (MMPs) in patients with NE from both the RT and the RM, suggesting leukocyte activation, extracellular matrix degradation, and leukocyte chemotaxis. Interestingly, levels of several cytokines were distinctly different between patients NE from the RT when compared with those from the RM. These differences were not related to the genetic variation of orthohantaviruses circulating in those regions, as sequence analysis showed that Puumala virus (PUUV) was the causative agent of NE in these regions. Additionally, only the “Russia” (RUS) genetic lineage of PUUV was detected in the serum samples of patients with NE from both the RT and the RM. We therefore conclude that differences in serum cytokine, chemokine, and MMP levels between the RT and the RM are related to environmental factors and lifestyle differences that influence individual immune responses to orthohantavirus infection.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cytokine, Chemokine, and Metalloprotease Activation in the Serum of Patients with Nephropathia Epidemica from the Republic of Tatarstan and the Republic of Mordovia, Russia

et al. 2021

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“…It is a major and direct cause of hemorrhagic fever with renal syndrome, characterized by fever, vascular hemorrhage, and renal failure. These conditions are collectively called hemorrhagic fever with renal syndrome (HFRS) [13]. This illness is among the most serious hemorrhagic diseases in the world, like Ebola hemorrhagic fever, and because of its high mortality rate, it is a major public health concern [14,15].…”

Section: Introductionmentioning

confidence: 99%

Insight into the Hantaan virus RNA-dependent RNA polymerase inhibition using in-silico approaches

et al. 2022

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The Hantaan virus (HTN) is a member of the hantaviridae family. It is a segmented type, negative-strand virus (sNSVs). It causes hemorrhagic fever with renal syndrome, which includes fever, vascular hemorrhage, and renal failure. This illness is one of the most serious hemorrhagic diseases in the world, and it is a major public health concern due to its high mortality rate. The Hantaan virus RNA-dependent RNA polymerase complex (RdRp) is involved in viral RNA transcription and replication for the survival and transmission of this virus. Therefore, it is a primary target for antiviral drug development. Interference with the endonucleolytic "cap-snatching" reaction by the HTN virus RdRp endonuclease domain is a particularly appealing approach for drug discovery against this virus. This RdRp endonuclease domain of the HTN virus has a metaldependent catalytic activity. We targeted this metal-dependent enzymatic activity to identify inhibitors that can bind and disrupt this endonuclease enzyme activity using in-silico approaches i.e., molecular docking, molecular dynamics simulation, predicted absorption, distribution, metabolism, excretion, toxicity (ADMET) and drug-likeness studies. The docking studies showed that peramivir, and ingavirin compounds can effectively bind with the manganese ions and engage with other active site residues of this protein. Molecular simulations also showed stable binding of these ligands with the active site of HTN RdRp. Simulation analysis showed that they were in constant contact with the active site manganese ions and amino acid residues of the HTN virus endonuclease domain. This study will help in better understanding the HTN and related viruses.

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Cross‐reactivity of hantavirus antibodies after immunization with PUUV antigens

Shkair,

Sharma,

Hamza

et al. 2024

Biotech and App Biochem

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Nephropathia epidemica (NE), caused by Puumala (PUUV) orthohantavirus, is endemic in the Republic of Tatarstan (RT). There are limited options for NE prevention in RT. Currently, available vaccines are made using Haantan (HNTV) orthohantavirus antigens. In this study, the efficacy of microvesicles (MVs) loaded with PUUV antigens to induce the humoral immune response in small mammals was analyzed. Additionally, the cross‐reactivity of serum from immunized small mammals and NE patients with HNTV, Dobrava, and Andes orthohantaviruses was investigated using nucleocapsid (N) protein peptide libraries. Finally, the selected peptides were analyzed for allergenicity, their ability to induce an autoimmune response, and their interaction with Class II HLA. Several N protein peptides were found to be cross‐reactive with serum from MVs immunized small mammals. These cross‐reactive epitopes were located in oligomerization perinuclear targeting and Daxx‐interacting domains. Most cross‐reactive peptides lack allergenic and autoimmune reactivity. Molecular docking revealed two cross‐reacting peptides, N6 and N19, to have good binding with three Class II HLA alleles. These peptides could be candidates for developing vaccines and therapeutics for NE.

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Hemorrhagic fever with renal syndrome: clinical, pathogenetic and therapeutic aspects

Cited by 4 publications

References 0 publications

Cytokine, Chemokine, and Metalloprotease Activation in the Serum of Patients with Nephropathia Epidemica from the Republic of Tatarstan and the Republic of Mordovia, Russia

Cytokine, Chemokine, and Metalloprotease Activation in the Serum of Patients with Nephropathia Epidemica from the Republic of Tatarstan and the Republic of Mordovia, Russia

Insight into the Hantaan virus RNA-dependent RNA polymerase inhibition using in-silico approaches

Cross‐reactivity of hantavirus antibodies after immunization with PUUV antigens

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