dc.contributor.author
Raftery, Martin J.
dc.contributor.author
Lalwani, Pritesh
dc.contributor.author
Lütteke, Nina
dc.contributor.author
Kobak, Lidija
dc.contributor.author
Giese, Thomas
dc.contributor.author
Ulrich, Rainer G.
dc.contributor.author
Radosa, Lukas
dc.contributor.author
Krüger, Detlev H.
dc.contributor.author
Schönrich, Günther
dc.date.accessioned
2020-08-04T11:38:09Z
dc.date.available
2020-08-04T11:38:09Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/27936
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-27689
dc.description.abstract
Members of different virus families including Hantaviridae cause viral hemorrhagic fevers (VHFs). The decisive determinants of hantavirus-associated pathogenicity are still enigmatic. Pathogenic hantavirus species, such as Puumala virus (PUUV), Hantaan virus (HTNV), Dobrava-Belgrade virus (DOBV), and Sin Nombre virus (SNV), are associated with significant case fatality rates. In contrast, Tula virus (TULV) only sporadically causes mild disease in immunocompetent humans and Prospect Hill virus (PHV) so far has not been associated with any symptoms. They are thus defined here as low pathogenic/apathogenic hantavirus species. We found that productive infection of cells of the mononuclear phagocyte system (MPS), such as monocytes and dendritic cells (DCs), correlated well with the pathogenicity of hantavirus species tested. HTNV (intermediate case fatality rates) replicated more efficiently than PUUV (low case fatality rates) in myeloid cells, whereas low pathogenic/apathogenic hantavirus species did not produce any detectable virus titers. Analysis of PHPUV, a reassortant hantavirus derived from a pathogenic (PUUV) and an apathogenic (PHV) hantavirus species, indicated that the viral glycoproteins are not decisive for replication in MPS cells. Moreover, blocking acidification of endosomes with chloroquine decreased the number of TULV genomes in myeloid cells suggesting a post-entry block for low pathogenic/apathogenic hantavirus species in myeloid cells. Intriguingly, pathogenic but not low pathogenic/apathogenic hantavirus species induced conversion of monocytes into inflammatory DCs. The proinflammatory programming of MPS cells by pathogenic hantavirus species required integrin signaling and viral replication. Our findings indicate that the capacity to replicate in MPS cells is a prominent feature of hantaviral pathogenicity.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
viral pathogenesis
en
dc.subject
dendritic cells
en
dc.subject
hantaviral entry
en
dc.subject
inflammatory DCs
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Replication in the Mononuclear Phagocyte System (MPS) as a Determinant of Hantavirus Pathogenicity
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
281
dcterms.bibliographicCitation.doi
10.3389/fcimb.2020.00281
dcterms.bibliographicCitation.journaltitle
Frontiers in Cellular and Infection Microbiology
dcterms.bibliographicCitation.originalpublishername
Frontiers Media S.A.
dcterms.bibliographicCitation.volume
10
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
32596167
dcterms.isPartOf.eissn
2235-2988