Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture

Abstract

Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China. The reservoir host of HTNV is field mouse (Apodemus agraricus). The main manifestation of HFRS, including acute kidney injury, increases vascular permeability, and coagulation abnormalities. In this paper, we review the current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors. Furthermore, the treatment and prevention will be discussed.

Keywords: Bunyavirus; hantaan virus; hantavirus; hemorrhagic fever with renal syndrome; pathogenesis.

Figure 1

Left side: Normal endothelial cells (EC), no vascular leakage occurs. Right side: EC were infected with hantaviruses. ZO-1, VEGFR2, VE-cadherin on EC were altered. High hantavirus RNA load result in severe vascular leakage. Virus-infected ECs be cleared by virus-specific CTLs leading to vascular damage. Owing to acute thrombocytopenia, there are not sufficient platelets available to repair “holes” in the EC barrier, resulting in vascular leakage. In addition, cytokines produced during the innate response against pathogenic hantaviruses like TNF-α could enhance vascular permeability.

Figure 2

Monocytes, macrophages, NK cells, and Lymphocytes produce various cytokines/chemokines which directly or indirectly increase vascular permeability. The humoral pattern recognition receptor PTX3 and antibodies activate complement. Activated complement components induce cytoskeletal rearrangement in EC further increasing dysfunction of the EC barrier. TLRs recognize Hantavirus and mediate the innate response. Virus-infected ECs were cleared by virus-specific CTLs leading to vascular leakage. B cells produce several subclass antibodies, while only the neutralizing antibodies against G1 and G2 is beneficial to decrease the viruses, then decrease vascular leakage.