Dataset Information

Characterization of the Puumala orthohantavirus Strains in the Northwestern Region of the Republic of Tatarstan in Relation to the Clinical Manifestations in Hemorrhagic Fever With Renal Syndrome Patients.

ABSTRACT: Over 1,000 cases of hemorrhagic fever with renal syndrome (HFRS) were recorded in the Republic of Tatarstan (RT) in 2015. HFRS is a zoonotic disease caused by several different Old World hantaviruses. In RT, Puumala orthohantavirus (PUUV) is a prevalent etiological agent of HFRS. We looked for the genetic link between the PUUV strains isolated from the bank voles and from the infected humans. In addition, possible correlation between the genetic makeup of the PUUV strain involved and different clinical picture of HFRS was investigated. Partial PUUV small (S) genome segment sequences were retrieved from 37 small animals captured in the northwestern region of RT in 2015. Phylogenetic analysis revealed that 34 PUUV sequences clustered with strains of the previously identified "Russia" (RUS) genetic lineage, while 3 remaining PUUV sequences clustered with the known lineage from Finland (FIN). Sequence comparisons showed that the majority of the S-segment sequences isolated in the current study displayed 98.2-100.0% sequence identity when compared with the strains isolated earlier from the HFRS patients hospitalized in Kazan city. HFRS patients infected with PUUV strains of either RUS or FIN genetic lineages were observed to have consistent differences in clinical presentation of the disease and laboratory findings. These findings indicated a strong genetic link between the infected bank voles and human HFRS cases from the same localities. Thus, S-segment sequences of the PUUV strains isolated from HFRS patients could serve as a molecular marker for determining the likely geographic area where infection occurred.

SUBMITTER: Davidyuk YN

PROVIDER: S-EPMC6739438 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Characterization of the <i>Puumala orthohantavirus</i> Strains in the Northwestern Region of the Republic of Tatarstan in Relation to the Clinical Manifestations in Hemorrhagic Fever With Renal Syndrome Patients.

Davidyuk Yuriy N YN Kabwe Emmanuel E Shakirova Venera G VG Martynova Ekaterina V EV Ismagilova Ruzilya K RK Khaertynova Ilsiyar M IM Khaiboullina Svetlana F SF Rizvanov Albert A AA Morzunov Sergey P SP

Frontiers in pharmacology 20190905

Over 1,000 cases of hemorrhagic fever with renal syndrome (HFRS) were recorded in the Republic of Tatarstan (RT) in 2015. HFRS is a zoonotic disease caused by several different Old World hantaviruses. In RT, <i>Puumala orthohantavirus</i> (PUUV) is a prevalent etiological agent of HFRS. We looked for the genetic link between the PUUV strains isolated from the bank voles and from the infected humans. In addition, possible correlation between the genetic makeup of the PUUV strain involved and diff ...[more]

PMID: 31543819

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Project description:BackgroundInfections with the Puumala orthohantavirus (PUUV) in humans may cause hemorrhagic fever with renal syndrome (HFRS), known as nephropathia epidemica (NE), which is associated with acute renal failure in severe cases. In response to PUUV-infections, a subset of potent antiviral NKG2C+ NK cells expand, whose role in virus defence and pathogenesis of NE is unclear. NKG2C+ NK cell proliferation is mediated by binding of NKG2C/CD94 to HLA-E on infected cells. The proliferation and activation of NKG2C+ NK cells via the NKG2C/HLA-E axis is affected by different NKG2C (NKG2Cwt/del) and HLA-E (HLA-E*0101/0103) alleles, which naturally occur in the human host. Homozygous (NKG2Cdel/del) and heterozygous (NKG2Cwt/del) deletions of the NKG2C receptor results in an impaired NKG2C/CD94 mediated proliferation and activation of NKG2C+ cells. We therefore analyzed the PUUV-mediated NKG2C+ NK cell responses and the impact of different NKG2C and HLA-E alleles in NE patients.Methodology/principal findingsNKG2C+ NK cell expansion and effector functions in PUUV-infected cells were investigated using flow cytometry and it was shown that PUUV-infected endothelial cells led to a NKG2C/CD94 mediated NKG2C+ NK cell activation and expansion, dependent on the HLA-G-mediated upregulation of HLA-E. Furthermore, the NKG2Cdel and HLA-E*0101/0103 alleles were determined in 130 NE patients and 130 matched controls, and it was shown that in NE patients the NKG2Cwt/del allele was significantly overrepresented, compared to the NKG2Cwt/wt variant (p = 0.01). In addition, in vitro analysis revealed that NKG2Cwt/del NK cells exhibited on overall a lower proliferation (p = 0.002) and lower IFNγ expression (p = 0.004) than NKG2Cwt/wt NK cells.Conclusions/significanceOur results corroborate the substantial impact of the NKG2C/HLA-E axis on PUUV-specific NK cell responses. A weak NKG2C+ NK cell response, as reflected by NKG2Cwt/del variant, may be associated with a higher risk for a severe hantavirus infections.

Dataset Information

Characterization of the Puumala orthohantavirus Strains in the Northwestern Region of the Republic of Tatarstan in Relation to the Clinical Manifestations in Hemorrhagic Fever With Renal Syndrome Patients.

Publications

Characterization of the <i>Puumala orthohantavirus</i> Strains in the Northwestern Region of the Republic of Tatarstan in Relation to the Clinical Manifestations in Hemorrhagic Fever With Renal Syndrome Patients.

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