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

Abstract

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.

Antiinflammatory phytochemicals against virus‐induced hyperinflammatory responses: Scope, rationale, application, and limitations

“…Simultaneous activation of the adaptive immune response through T H and T C cells, and subsequent secretion of interleukin (IL)‐12 and IL‐4‐dependent signaling provides effective Th1/Th2 balance against invading pathogens (Nash & Dutia, 2010). However, the dysregulated immune response has been reported in several viral infections such as influenza, Ebola, hantavirus, and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) which leads to severe symptoms such as anaphylactic shock, trauma, local tissue damage, and multi‐organ failure (Jain, Khaiboullina, & Baranwal, 2020; Martynova et al, 2021; Tang et al, 2020; Tisoncik et al, 2012; Younan et al, 2017). Subjects with comorbidities such as obesity, cardiometabolic diseases, type II diabetes, and non‐alcoholic fatty liver disease with underlying chronic “low‐grade” inflammation are at higher risk of hyperimmune response during viral infections.…”

Serum Markers Associated with Disease Severity in a Bosnian Hemorrhagic Fever with Renal Syndrome Cohort

“…This retrospective PUUV patient cohort study aimed to identify biomarkers associated with more severe disease in terms of platelet count and kidney injury. IL-18 is an important pro-inflammatory cytokine often found to be upregulated in PUUV patients compared to healthy controls, indicating a role in pathogenesis [ 12 , 13 , 14 , 15 ]. In the current study, IL-18 was significantly higher in patients in the low platelet group.…”

Cells of the human respiratory tract support the replication of pathogenic Old World orthohantavirus Puumala

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