Usutu Virus: An Emerging Flavivirus in Europe

Ashraf, Usama; Ye, Jing; Ruan, Xindi; Wan, Shengfeng; Zhu, Bibo; Cao, Shengbo

doi:10.3390/v7010219

Cited by 133 publications

(114 citation statements)

References 77 publications

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“…Many viruses, including Usutu virus, West Nile virus, Japanese encephalitis virus, influenza virus and enterovirus, exhibit altered pathogenesis that is due to amino acid substitutions at specific positions in viral proteins (Chambers et al, 1998;Ashraf et al, 2015;Gromowski et al, 2015;Han et al, 2015;Kataoka et al, 2015). This phenomenon has also been documented in the fish virus VHSV, showing that a single amino acid substitution in the L protein resulted in the change of viral virulence to rainbow trout gill epithelial cells (Kim et al, 2014).…”

Section: Conclusion and Future Aspectsmentioning

confidence: 99%

Spring viraemia of carp virus: recent advances

Ashraf

Lin

et al. 2016

Journal of General Virology

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182

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Section: Conclusion and Future Aspectsmentioning

confidence: 99%

Spring viraemia of carp virus: recent advances

Ashraf

Lin

et al. 2016

Journal of General Virology

Self Cite

182

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“…Furthermore, infection by Usutu virus (USUV; a related emerging flavivirus [22]) was also inhibited by the drugs used. Our results point to ACC as a potential druggable antiviral target against WNV and related flaviviruses.…”

mentioning

confidence: 99%

Modification of the Host Cell Lipid Metabolism Induced by Hypolipidemic Drugs Targeting the Acetyl Coenzyme A Carboxylase Impairs West Nile Virus Replication

Merino-Ramos

Vázquez-Calvo

Casas

et al. 2016

Antimicrob Agents Chemother

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West Nile virus (WNV) is a mosquito-borne neurotropic flavivirus responsible for recurrent outbreaks of meningitis and encephalitis affecting humans, horses, and birds in Africa, Europe, Asia, Oceania, and America (1). A great effort has been devoted in the past several years to decipher the molecular biology of WNV and its interaction with the host immune system (2, 3). Nevertheless, no licensed vaccine or therapy for human use against this pathogen is yet available.The flavivirus life cycle (including that of WNV) is intimately associated with host cell lipids. The replication of the viral genomic RNA and flavivirus nascent virion assembly take place in modified membranes from the endoplasmic reticulum (4-7). To build an adequate microenvironment to support viral replication and particle biogenesis, flaviviruses rearrange host cell lipid metabolism by promoting the synthesis and accumulation of specific cellular lipids (i.e., fatty acids, glycerophospholipids [GPLs], sphingolipids [SLs], and cholesterol) (8-15). This makes the pharmacological manipulation of cellular lipids an attractive antiviral strategy against WNV and related flaviviruses (13,14,16,17).The first steps of lipid biogenesis involve the synthesis and elongation of fatty acids, which provide the building blocks for the synthesis of more-complex lipids. Hence, fatty acid synthesis and elongation have become key targets for antiviral therapy (13,18,19). Regarding the flaviviruses, the pharmacological blockage of the fatty acid synthase FASN (which catalyzes the synthesis of palmitate from acetyl coenzyme A [acetyl-CoA] and malonylCoA into long-chain saturated fatty acids) reduced the viral replication (11, 13). The enzyme preceding FASN in the fatty acid biosynthetic route is the acetyl-CoA carboxylase (ACC), which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA. Due to its rate-limiting role in fatty acid synthesis, ACC is currently a target of increasing interest within the pharmacological industry (20, 21). However, to our knowledge, the involvement of ACC in the replication of WNV, or other related flaviviruses, has not yet been evaluated.In this work, we have shown that ACC inhibitors alter the cellular lipid composition and reduce the levels of WNV infection in cultured cells. Furthermore, infection by Usutu virus (USUV; a related emerging flavivirus [22]) was also inhibited by the drugs used. Our results point to ACC as a potential druggable antiviral target against WNV and related flaviviruses. MATERIALS AND METHODSCells, viruses, infections, and virus titrations. All infectious virus manipulations were performed in biosafety level 3 (BSL-3) facilities. Vero, HeLa, and Neuro2a (N2a) cell lines were cultured as described previously (10, 23). Cells were incubated with the corresponding virus, WNV strain NY99 or USUV strain SAAR-1776 (24), for 1 h at 37°C; viral inoculum was removed; and infected cells were incubated in culture medium containing 1% fetal bovine serum (time that was considered 1 h postinfection [p.i.]).

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“…In nature, these viruses maintain a life cycle in vertebrates and/or arthropods, but accidental introduction into a new life cycle in humans results in unexpected diseases (48). The ability of the virus to cross the species barrier is a complex multifactorial process, and our understanding of the molecular basis of the pathogenesis of severe disease remains inadequate.…”

Section: Discussionmentioning

confidence: 99%

The Emerging Duck Flavivirus Is Not Pathogenic for Primates and Is Highly Sensitive to Mammalian Interferon Antiviral Signaling

Wang

Liu

et al. 2016

J Virol

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Flaviviruses pose a significant threat to both animals and humans. Recently, a novel flavivirus, duck Tembusu virus (DTMUV), was identified to be the causative agent of a serious duck viral disease in Asia. Its rapid spread, expanding host range, and uncertain transmission routes have raised substantial concerns regarding its potential threats to nonavian hosts, including humans. Here, we demonstrate that DTMUV is not pathogenic for nonhuman primates and is highly sensitive to mammal type I interferon (IFN) signaling. In vitro assays demonstrated that DTMUV infected and replicated efficiently in various mammalian cell lines. Further tests in mice demonstrated high neurovirulence and the age-dependent neuroinvasiveness of the virus. In particular, the inoculation of DTMUV into rhesus monkeys did not result in either viremia or apparent clinical symptoms, although DTMUV-specific humoral immune responses were detected. Furthermore, we revealed that although avian IFN failed to inhibit DTMUV in avian cells, DTMUV was more sensitive to the antiviral effects of type I interferon than other known human-pathogenic flaviviruses. Knockout of the type I IFN receptor in mice caused apparent viremia, viscerotropic disease, and mortality, indicating a vital role of IFN signaling in protection against DTMUV infection. Collectively, we provide direct experimental evidence that this novel avian-origin DTMUV possesses a limited capability to establish infection in immunocompetent primates due to its decreased antagonistic activity in the mammal IFN system. Furthermore, our findings highlight the potential risk of DTMUV infection in immunocompromised individuals and warrant studies on the cross-species transmission and pathogenesis of this novel flavivirus. IMPORTANCEMosquito-borne flaviviruses comprise a large group of pathogenic and nonpathogenic members. The pathogenic flaviviruses include dengue, West Nile, and Japanese encephalitis viruses, and the nonpathogenic flaviviruses normally persist in a natural cycle and rarely cause disease in humans. A novel flavivirus, DTMUV (also known as duck egg drop syndrome flavivirus [DEDSV]) was identified in 2012 in ducks and then rapidly spread to several Asian countries. This new flavivirus was then shown to infect multiple avian species, resulting in neurological symptoms with unknown routes of transmission. There is public concern regarding its potential transmission from birds to humans and other nonavian hosts. Our present study shows that the mammalian IFN system can efficiently eliminate DTMUV infection and that the emergence of severe DTMUV-associated disease in mammals, especially humans, is unlikely. Currently, DTMUV infection mostly affects avian species.T he genus Flavivirus of the family Flaviviridae contains emerging and reemerging enveloped RNA viruses that cause serious diseases in humans and animals, including dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV). A group ...

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Usutu Virus: An Emerging Flavivirus in Europe

Cited by 133 publications

References 77 publications

Spring viraemia of carp virus: recent advances

Spring viraemia of carp virus: recent advances

Modification of the Host Cell Lipid Metabolism Induced by Hypolipidemic Drugs Targeting the Acetyl Coenzyme A Carboxylase Impairs West Nile Virus Replication

The Emerging Duck Flavivirus Is Not Pathogenic for Primates and Is Highly Sensitive to Mammalian Interferon Antiviral Signaling

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