Usutu virus disease: a potential problem for North America?

Gill, Christine M.; Kapadia, Ronak K.; Beckham, J. David; Piquet, Amanda L.; Tyler, Kenneth L.; Pastula, Daniel M.

doi:10.1007/s13365-019-00818-y

Cited by 12 publications

(11 citation statements)

References 48 publications

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“…Usutu virus (USUV) is an emerging zoonotic virus that can cause neuroinvasive disease in humans [1]. As a member of the Flaviviridae family, Flavivirus genus, USUV is closely related to other pathogens of global human health concern, including West Nile virus (WNV), dengue virus (DENV), yellow fever virus (YFV), and Zika virus (ZIKV) [2].…”

Section: Introductionmentioning

confidence: 99%

Differential pathogenesis of Usutu virus isolates in mice

et al. 2020

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Usutu virus (USUV; Flavivirus), a close phylogenetic and ecological relative of West Nile virus, is a zoonotic virus that can cause neuroinvasive disease in humans. USUV is maintained in an enzootic cycle between Culex mosquitoes and birds. Since the first isolation in 1959 in South Africa, USUV has spread throughout Africa and Europe. Reported human cases have increased over the last few decades, primarily in Europe, with symptoms ranging from mild febrile illness to severe neurological effects. In this study, we investigated whether USUV has become more pathogenic during emergence in Europe. Interferon α/β receptor knockout (Ifnar1-/-) mice were inoculated with recent USUV isolates from Africa and Europe, as well as the historic 1959 South African strain. The three tested African strains and one European strain from Spain caused 100% mortality in inoculated mice, with similar survival times and histopathology in tissues. Unexpectedly, a European strain from the Netherlands caused only 12% mortality and significantly less histopathology in tissues from mice compared to mice inoculated with the other strains. Viremia was highest in mice inoculated with the recent African strains and lowest in mice inoculated with the Netherlands strain. Based on phylogenetics, the USUV isolates from Spain and the Netherlands were derived from separate introductions into Europe, suggesting that disease outcomes may differ for USUV strains circulating in Europe. These results also suggest that while more human USUV disease cases have been reported in Europe recently, circulating African USUV strains are still a potential major health concern.

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Section: Introductionmentioning

confidence: 99%

Differential pathogenesis of Usutu virus isolates in mice

et al. 2020

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“…The mosquito-borne Usutu virus (USUV) is an emerging zoonotic flavivirus (Simmonds et al, 2017) and within the family Flaviviridae it belongs to the Japanese encephalitis virus serogroup together with West Nile virus (WNV). USUV is currently circulating in Africa, the Middle East, and Europe (Gill et al, 2020). In multiple European countries its presence was already documented by various methods of detection of viral RNA and of anti-USUV antibodies (Vilibic-Cavlek et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the current circulation of USUV in a specific geographic area could serve as an indicator for WNV (Nikolay, 2015). Additionally, some of the virological features and clinical characteristics are similar between USUV and WNV suggesting the study of USUV as a reference for WNV (Nikolay, 2015;Gill et al, 2020). No vaccines or anti-viral treatment options are available so far for USUV disease (Gill et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

The Interferon Response Dampens the Usutu Virus Infection-Associated Increase in Glycolysis

Wald

Sieg

Schilling

et al. 2022

Front. Cell. Infect. Microbiol.

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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) β. 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.

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“…Its synonymous virus, ITV, also re-emerged in Israel in the same time period (22). Likewise, in other areas of the world, similar patterns of flavivirus emergence are being observed, particularly involving those belonging to the JE and Ntaya groups (7,23,24). Also, the risk of emergence of any of those viruses in distant territories should not be disregarded, as some members of these groups have demonstrated their capacity to undergo transcontinental displacements.…”

Section: Introductionmentioning

confidence: 88%