Puumala and Tula Virus Differ in Replication Kinetics and Innate Immune Stimulation in Human Endothelial Cells and Macrophages.

Bourquain Bourquain,Schürer Schürer,Schaade Schaade,Bodenstein Bodenstein

doi:10.3390/v11090855

Abstract

Old world hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) upon zoonotic transmission to humans. In Europe, the Puumala virus (PUUV) is the main causative agent of HFRS. Tula virus (TULV) is also widely distributed in Europe, but there is little knowledge about the pathogenicity of TULV for humans, as reported cases are rare. We studied the replication of TULV in different cell types in comparison to the pathogenic PUUV and analyzed differences in stimulation of innate immunity. While both viruses replicated to a similar extent in interferon (IFN)-deficient Vero E6 cells, TULV replication in human lung epithelial (A549) cells was slower and less efficient when compared to PUUV. In contrast to PUUV, no replication of TULV could be detected in human microvascular endothelial cells and in macrophages. While a strong innate immune response towards PUUV infection was evident at 48 h post infection, TULV infection triggered only a weak IFN response late after infection of A549 cells. Using appropriate in vitro cell culture models for the orthohantavirus infection, we could demonstrate major differences in host cell tropism, replication kinetics, and innate immune induction between pathogenic PUUV and the presumably non- or low-pathogenic TULV that are not observed in Vero E6 cells and may contribute to differences in virulence.

Highlights

Hantaviruses are three segmented negative-stranded RNA viruses which are harbored by small mammals
We compared the replication of Tula virus (TULV) and Puumala virus (PUUV) in human epithelial and endothelial cells, as well as in cells of the monocyte–macrophage lineage
The cells were infected with a multiplicity of infection (MoI) of 0.1 and viral RNA concentrations in the cell culture supernatants were quantified via quantitative reverse transcription (qRT)-PCR at 0 h to 6 d p.i. (Figure 1)

Summary

Introduction

Hantaviruses are three segmented negative-stranded RNA viruses which are harbored by small mammals. They form the genus Orthohantavirus within the Hantaviridae family of the order Bunyavirales. Upon zoonotic transmission to humans via aerosols, they cause a disease known as hemorrhagic fever with renal syndrome (HFRS) in the old world and hantavirus cardiopulmonary syndrome (HCPS) in the new world [1]. Hantavirus-associated diseases in Europe are mainly caused by infections with Puumala virus (PUUV) carried by Myodes voles and to a lesser extent by Dobrava-Belgrade virus (DOBV) carried by different Apodemus species [2]. While PUUV causes mainly a mild form of HFRS, known as nephropathia epidemica [3], DOBV infections tend to be more severe [2,4]. TULV infection in humans has been serologically documented in blood donors in the Czech Republic [8]

Methods

Results

Conclusion