Suchergebnisse

Phleboviruses (order Bunyavirales, family Phenuiviridae) are globally emerging arboviruses with a wide spectrum of virulence. Sandfly fever Sicilian virus (SFSV) is one of the most ubiquitous members of the genus Phlebovirus and associated with a self-limited, incapacitating febrile disease in travellers and military troops. The phleboviral NSs protein is an established virulence factor, acting as antagonist of the antiviral interferon (IFN) system. Consistently, we previously reported that SFSV NSs targets the induction of IFN mRNA synthesis by specifically binding to the DNA-binding domain of the IFN transcription factor IRF3. Here, we further characterized the effect of SFSV and its NSs towards IFN induction, and evaluated its potential to affect the downstream IFN-stimulated signalling and the subsequent transactivation of antiviral interferon-stimulated genes (ISGs). We found that SFSV dampened, but did not entirely abolish type I and type III IFN induction. Furthermore, SFSV NSs did not affect IFN signalling, resulting in substantial ISG expression in infected cells. Hence, although SFSV targets IRF3 to reduce IFN induction, it is not capable of entirely disarming the IFN system in the presence of high basal IRF3 and/or IRF7 levels, and we speculate that this significantly contributes to its low level of virulence.

16 Pàg. ; This work was supported by grants S2013/ABI-2906 (PLATESA), P2018/BAA-4370 (PLATESA2) from Comunidad de Madrid/FEDER and AGL2017-83326-R from Ministerio de Economía y Competitividad and PdC2021-121717-I00 funded by MCIN/AEI /10.13039/501100011033 and by Unión Europea Next Generation EU/ PRTR. AL-V has a pre-doctoral fellowship FPI 2017, Ministerio de Ciencia, Innovación y Universidades from the Spanish government. ; Peer reviewed

Abstract
The new variant of concern (VOC) of SARS-CoV-2, Omicron (B.1.1.529), is genetically very different from other VOCs. We compared Omicron with the preceding VOC Delta (B.1.617.2) and the wildtype (wt) strain (B.1) with respect to their interactions with the antiviral interferon (IFN-alpha/beta) response in infected cells. Our data indicate that IFN induction by Omicron is low and comparable to the wt, whereas Delta showed an increased IFN induction. However, Omicron exceeded both the wt and the Delta strain with respect to the ability to withstand the antiviral state imposed by IFN-alpha.

WOS: 000388677600001 ; PubMed ID: 27667586 ; In countries from which Crimean-Congo haemorrhagic fever (CCHF) is absent, the causative virus, CCHF virus (CCHFV), is classified as a hazard group 4 agent and handled in containment level (CL)-4. In contrast, most endemic countries out of necessity have had to perform diagnostic tests under biosafety level (BSL)-2 or -3 conditions. In particular, Turkey and several of the Balkan countries have safely processed more than 100 000 samples over many years in BSL-2 laboratories. It is therefore advocated that biosafety requirements for CCHF diagnostic procedures should be revised, to allow the tests required to be performed under enhanced BSL-2 conditions with appropriate biosafety laboratory equipment and personal protective equipment used according to standardized protocols in the countries affected. Downgrading of CCHFV research work from CL-4, BSL-4 to CL-3, BSL-3 should also be considered. ; European Commission under Health Cooperation Work Program of 7th Framework Program [260427] ; Funding was received through CCH Fever Network (Collaborative Project) supported by the European Commission under the Health Cooperation Work Program of the 7th Framework Program (grant agreement no. 260427) (http://www.cch-fever.eu/). The views expressed by state-employed American co-authors are their personal views, and do not necessarily represent the views of the US government agencies they work for. The views expressed by the ECDC coauthor are his personal views, and do not necessarily represent the views of the European agency he is working for.