Hantaan virus-induced elevation of plasma osteoprotegerin and its clinical implications in hemorrhagic fever with renal syndrome

Objectives: The bleeding tendency is a hallmark of hemorrhagic fever with renal syndrome (HFRS) after Hantaan virus (HTNV) infection. Growing reports indicate the importance of osteoprotegerin (OPG) in vascular homeostasis, implying OPG might be involved in the pathogenesis of coagulopathy in patients with HFRS.Methods: Acute and convalescence plasmas of 32 patients with HFRS were collected. Enzyme-linked immunosorbent assays (ELISA) were used to detect plasma OPG levels and other parameters. The human umbilical vein endothelial cells were stimulated with HTNV and/or tumor necrosis factor- alpha (TNF- alpha) to explore the source of OPG.Results: Plasma OPG levels of patients with HFRS were elevated and correlated positively with the severity of HFRS and negatively with platelet counts. Abundant OPG was released from endothelial cells in response to TNF- alpha stimuli, along with HTNV infection, which was in accordance with the findings of positive correlations between plasma OPG and TNF- alpha or c-reactive protein. Importantly, plasma OPG levels correlated positively with activated partial thromboplastin time and the content of d-dimer.Conclusion: These findings suggested that increased plasma OPG levels induced by HTNV might be an important factor for the severity of HFRS, and was likely involved in endothelium dysfunction and hemorrhagic disorder of HFRS, which might contribute to the pathogenesis of hemorrhage in HFRS.(c) 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study found that plasma OPG levels were elevated in patients with HFRS and correlated positively with disease severity and negatively with platelet counts. Endothelial cells released abundant OPG in response to TNF-α stimuli and HTNV infection, which correlated positively with plasma TNF-α and c-reactive protein. Increased plasma OPG levels induced by HTNV may be an important factor for the severity of HFRS and could contribute to endothelial dysfunction and hemorrhagic disorder.