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

• Verfasst von: Solà-Riera, Carles [VerfasserIn]
• Verfasst von: Gupta, Shawon [VerfasserIn]
• Titel: Orthohantaviruses belonging to three phylogroups all inhibit apoptosis in infected target cells
• Verf.angabe: Carles Solà-Riera, Shawon Gupta, Hans-Gustaf Ljunggren & Jonas Klingström
• E-Jahr: 2019
• Jahr: 29 January 2019
• Umfang: 11 S.
• Fussnoten: Gesehen am 25.02.2019
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2019
• Band/Heft Quelle: 9(2019) Artikel-Nummer 834, 11 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/s41598-018-37446-1
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1588004201

Abstract

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.