Nlrc3 Knockout Mice Showed Renal Pathological Changes After HTNV Infection.

Ruixue Ma,Shiyuan Hou,Jiayi Shu,Wenjie Sun,Xiaoxiao Zhang,Ziyu Liu,Fang Wang,Xia Jin,Yunhua Lv,Rongrong Liu,Xingan Wu,Qikang Ying

doi:10.3389/fimmu.2021.692509

Abstract

Hantaan virus (HTNV) infects humans and causes hemorrhagic fever with renal syndrome (HFRS). The development of well-characterized animal models of HFRS could accelerate the testing of vaccine candidates and therapeutic agents and provide a useful tool for studying the pathogenesis of HFRS. Because NLRC3 has multiple immunoregulatory roles, we investigated the susceptibility of Nlrc3−/− mice to HTNV infection in order to establish a new model of HFRS. Nlrc3−/− mice developed weight loss, renal hemorrhage, and tubule dilation after HTNV infection, recapitulating many clinical symptoms of human HFRS. Moreover, infected Nlrc3−/− mice showed higher viral loads in serum, spleen, and kidney than wild type C57BL/6 (WT) mice, and some of them manifested more hematological disorders and significant pathological changes within multiple organs than WT mice. Our results identify that HTNV infected Nlrc3−/− mice can develop clinical symptoms and pathological changes resembling patients with HFRS, suggesting a new model for studying the pathogenesis and testing of candidate vaccines and therapeutics.

Highlights

Hemorrhagic fever with renal syndrome (HFRS) presents acute interstitial nephropathy after zoonotic transmission of hantaviruses from rodents to humans
To characterize the susceptibility of Nlrc3−/− mice to Hantaan virus (HTNV) infection, a group of Nlrc3−/− mice were intraperitoneally infected with 5×105 Plaque-forming units (PFUs) of HTNV per mouse, using wild type C57BL/6 (WT) mice as controls
Results showed that PLT counts in WT mice decreased on 3dpi and gradually recovered, but they continued to decrease in Nlrc3−/− mice until reaching the lowest value on 9 dpi, significantly lower than that in WT on 9 dpi (P

Summary

Introduction

Hemorrhagic fever with renal syndrome (HFRS) presents acute interstitial nephropathy after zoonotic transmission of hantaviruses from rodents to humans. HFRS occurs with characteristics of high fever, hypotension, renal failure, and hemorrhage [4]. It can be divided into five clinical stages: febrile, hypotensive shock, oliguric, diuretic, and convalescent. An acute episode of HTNV infection leading to HFRS is often accompanied by thrombocytopenia, leukocytosis, anemia, elevated serum creatinine, and liver enzymes [5]. These clinical symptoms and signs can partly be explained by the fact that HTNV principally attacks the

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Results

Conclusion