Orthohantaviruses belonging to three phylogroups all inhibit apoptosis in infected target cells

Orthohantaviruses, previously known as hantaviruses, are zoonotic viruses that can cause hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS) in humans. The HPS-causing Andes virus (ANDV) and the HFRS-causing Hantaan virus (HTNV) have anti-apoptotic effects. To invest...

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Veröffentlicht in:Scientific reports Jg. 9; H. 1; S. 834
Hauptverfasser: Solà-Riera, Carles, Gupta, Shawon, Ljunggren, Hans-Gustaf, Klingström, Jonas
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 29.01.2019
Nature Publishing Group
Schlagworte:
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Apoptosis
Caspase
Caspase-3
Cytotoxicity
Endothelial cells
Fever
Granzyme B
Hantavirus
Hantavirus pulmonary syndrome
Hemorrhage
Hemorrhagic fever with renal syndrome
Humanities and Social Sciences
multidisciplinary
N protein
Nucleocapsids
Science
Science (multidisciplinary)
Staurosporine
Viruses
Zoonoses
ISSN:2045-2322, 2045-2322
Online-Zugang:Volltext
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Zusammenfassung:Orthohantaviruses, previously known as hantaviruses, are zoonotic viruses that can cause hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS) in humans. The HPS-causing Andes virus (ANDV) and the HFRS-causing Hantaan virus (HTNV) have anti-apoptotic effects. To investigate if this represents a general feature of orthohantaviruses, we analysed the capacity of six different orthohantaviruses – belonging to three distinct phylogroups and representing both pathogenic and non-pathogenic viruses – to inhibit apoptosis in infected cells. Primary human endothelial cells were infected with ANDV, HTNV, the HFRS-causing Puumala virus (PUUV) and Seoul virus, as well as the putative non-pathogenic Prospect Hill virus and Tula virus. Infected cells were then exposed to the apoptosis-inducing chemical staurosporine or to activated human NK cells exhibiting a high cytotoxic potential. Strikingly, all orthohantaviruses inhibited apoptosis in both settings. Moreover, we show that the nucleocapsid (N) protein from all examined orthohantaviruses are potential targets for caspase-3 and granzyme B. Recombinant N protein from ANDV, PUUV and the HFRS-causing Dobrava virus strongly inhibited granzyme B activity and also, to certain extent, caspase-3 activity. Taken together, this study demonstrates that six different orthohantaviruses inhibit apoptosis, suggesting this to be a general feature of orthohantaviruses likely serving as a mechanism of viral immune evasion.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-37446-1