Dengue and Zika Virus Capsid Proteins Contain a Common PEX19-Binding Motif
1
School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK
2
The Pirbright Institute, Pirbright GU24 0NF, UK
*
Authors to whom correspondence should be addressed.
Academic Editor: Angela L. Rasmussen
Viruses 2022, 14(2), 253; https://doi.org/10.3390/v14020253
Received: 9 December 2021
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Revised: 15 January 2022
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Accepted: 20 January 2022
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Published: 27 January 2022
(This article belongs to the Special Issue Host Factors in Viral Infections)
Flaviviruses such as dengue virus (DENV) and Zika virus (ZIKV) have evolved sophisticated mechanisms to suppress the host immune system. For instance, flavivirus infections were found to sabotage peroxisomes, organelles with an important role in innate immunity. The current model suggests that the capsid (C) proteins of DENV and ZIKV downregulate peroxisomes, ultimately resulting in reduced production of interferons by interacting with the host protein PEX19, a crucial chaperone in peroxisomal biogenesis. Here, we aimed to explore the importance of peroxisomes and the role of C interaction with PEX19 in the flavivirus life cycle. By infecting cells lacking peroxisomes we show that this organelle is required for optimal DENV replication. Moreover, we demonstrate that DENV and ZIKV C bind PEX19 through a conserved PEX19-binding motif, which is also commonly found in cellular peroxisomal membrane proteins (PMPs). However, in contrast to PMPs, this interaction does not result in the targeting of C to peroxisomes. Furthermore, we show that the presence of C results in peroxisome loss due to impaired peroxisomal biogenesis, which appears to occur by a PEX19-independent mechanism. Hence, these findings challenge the current model of how flavivirus C might downregulate peroxisomal abundance and suggest a yet unknown role of peroxisomes in flavivirus biology.
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Keywords:
peroxisomes; human peroxin PEX19; flavivirus; dengue virus; Zika virus; capsid protein
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MDPI and ACS Style
Farelo, M.A.; Korrou-Karava, D.; Brooks, K.F.; Russell, T.A.; Maringer, K.; Mayerhofer, P.U. Dengue and Zika Virus Capsid Proteins Contain a Common PEX19-Binding Motif. Viruses 2022, 14, 253. https://doi.org/10.3390/v14020253
AMA Style
Farelo MA, Korrou-Karava D, Brooks KF, Russell TA, Maringer K, Mayerhofer PU. Dengue and Zika Virus Capsid Proteins Contain a Common PEX19-Binding Motif. Viruses. 2022; 14(2):253. https://doi.org/10.3390/v14020253
Chicago/Turabian StyleFarelo, Mafalda A., Despoina Korrou-Karava, Katrina F. Brooks, Tiffany A. Russell, Kevin Maringer, and Peter U. Mayerhofer. 2022. "Dengue and Zika Virus Capsid Proteins Contain a Common PEX19-Binding Motif" Viruses 14, no. 2: 253. https://doi.org/10.3390/v14020253
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