The Presence of Circulating Nucleated Red Blood Cells Is Associated With Disease Severity in Patients of Hemorrhagic Fever With Renal Syndrome.

Jingang Zhang,Yun Zhang,Meng Wang,Haifeng Hu,Boquan Jin,Xiaozhou Jia,Yusi Zhang,Kang Tang,Ying Ma,Xiyue Zhang,Chunmei Zhang,Dalu Liu,Ran Zhuang

doi:10.3389/fmed.2021.665410

Abstract

Hemorrhagic fever with renal syndrome (HFRS) is a regional infectious disease of epidemic potential caused by the Hantaan virus (HTNV). Red blood cells (RBCs) are the major components of peripheral blood. However, pathological changes in RBCs and the underlying mechanisms during HTNV infection remain largely unclear. Therefore, this study sought to explore changes in RBCs in the peripheral blood of HFRS patients. We isolated PBMCs from HFRS patients and performed single-cell RNA sequencing. The results showed that clusters of RBCs in the peripheral blood of HFRS could be classified as nucleated red blood cells (NRBC) based on their cellular components, gene expression profiles and cell surface markers. In addition, it was shown that the higher the count of NRBC in peripheral blood, the more severe the disease status was. Moreover, hematological indices related to RBCs were analyzed and the results showed that impairment in the folate pathway might be the possible reason behind the presence of NRBCs. This study, for the first time showed that the presence of NRBCs in the peripheral blood of HFRS patients was associated with disease severity. This was also the first study to show that infection with the HTNV virus hindered the maturation of RBCs. Therefore, this work provides further insights on the role of and pathological changes in RBCs during HTNV infection.

Highlights

Hemorrhagic fever with renal syndrome (HFRS) is caused by infection with the Hantaan virus (HTNV) and has resulted to epidemics throughout Eurasia
Red Blood Cells Shown in peripheral blood mononuclear cells (PBMCs) of HFRS Patients
The results suggested that nucleated red blood cells (NRBC) in the PBMCs from HFRS patients displayed antiviral responses

Summary

Introduction

Hemorrhagic fever with renal syndrome (HFRS) is caused by infection with the Hantaan virus (HTNV) and has resulted to epidemics throughout Eurasia. NRBCs in HFRS Patients killer cells have been well-studied during HTNV infection [2,3,4,5,6]. RBCs are developed within the bone marrow through the process of erythropoiesis which involves a series of maturation steps. During this process, multipotent hematopoietic stem cells differentiate into erythroid progenitor cells. Thereafter, nucleated precursors differentiate from proerythroblasts into basophilic, polychromatic and orthochromatic erythroblasts [7, 8] These stages result to the accumulation of hemoglobin (HGB) [9]. Given the maturation process of RBCs, the nucleated red blood cells (NRBCs) should remain in the bone marrow of healthy adults except for certain physiological or pathological conditions where they become visible

Methods

Results

Conclusion