The mosquito-borne Usutu virus (USUV) is a zoonotic flavivirus and an emerging
pathogen. So far therapeutical options or vaccines are not available in human and
veterinary medicine. The bioenergetic profile based on extracellular flux analysis
revealed an USUV infection-associated significant increase in basal and stressed
glycolysis on Vero and with a tendency for basal glycolysis on the avian cell line TME-R
derived from Eurasian blackbirds. On both cell lines this was accompanied by a significant
drop in the metabolic potential of glycolysis. Moreover, glycolysis contributed to
production of virus progeny, as inhibition of glycolysis with 2-deoxy-D-glucose reduced
virus yield on Vero by one log10 step. Additionally, the increase in glycolysis observed on
Vero cells after USUV infection was lost after the addition of exogenous type I interferon
(IFN) b. To further explore the contribution of the IFN response pathway to the impact of
USUV on cellular metabolism, USUV infection was characterized on human A549
respiratory cells with a knockout of the type I IFN receptor, either solely or together with
the receptor of type III IFN. Notably, only the double knockout of types I and III IFN receptor
increased permissiveness to USUV and supported viral replication together with an
alteration of the glycolytic activity, namely an increase in basal glycolysis to an extent
that a further increase after injection of metabolic stressors during extracellular flux
analysis was not noted. This study provides evidence for glycolysis as a possible target
for therapeutic intervention of USUV replication. Moreover, presented data highlight type I
and type III IFN system as a determinant for human host cell permissiveness and for the
infection-associated impact on glycolysis.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84536 |
| Date | 03 April 2023 |
| Creators | Wald, Maria Elisabeth, Sieg, Michael, Schilling, Erik, Binder, Marco, Vahlenkamp, Thomas Wilhelm, Claus, Claudia |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2235-2988, 823181 |
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