NK Cells Were Activated and Involved in the Physiopathology of Hemorrhagic Fever with Renal Syndrome

Abstract

As a key component of innate immunity, natural killer (NK) cells initiate rapid effector responses against various viral pathogens. However, their role in the pathogenesis of hemorrhagic fever with renal syndrome (HFRS) remains unclear. In this study, NK cell subsets and receptor expression were analyzed by flow cytometry in patients with HFRS. Enzyme-linked immunosorbent assay was used to measure soluble HLA-G (sHLA-G) levels in plasma. In experimental models of acute viral infection, changes in the expression of several NK cell receptor ligands were also detected by flow cytometry. Flow cytometry revealed a redistribution of NK cell subsets in patients with HFRS, characterized by the expansion of CD56⁺CD16⁻ NK cells, which remained elevated from the acute phase to the convalescent phase. In addition, sustained overexpression of NK cell receptors (NCR p30⁺, NCR p44⁺, NCR p46⁺, KIR2DL2/3, and KIR2DL4) was observed beyond the acute phase. Higher plasma concentrations of sHLA-G were detected in mild-type cases compared with moderate-type, severe-type, and critical-type patients. Hantaan virus infection was also found to upregulate intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD62E, CD62P, human leukocyte antigen-A, B, C (HLA-A, B, C), HLA-E, and HLA-G. These findings suggest that NK cells undergo rapid expansion following viral infection and maintain elevated levels throughout the clinical course, accompanied by persistent overexpression of NK receptors. Lower concentrations of soluble HLA-G (sHLA-G) in moderate-type, severe-type, and critical-type patients may indicate a potential mechanism contributing to increased vascular permeability in HFRS.