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Confirmatory Results

Zika Virus Capsid Anchor Forms Cytotoxic Amyloid-like Fibrils

Kumar Udit Saumya, Kundlik Gadhave, Amit Kumar, Rajanish Giri
doi: https://doi.org/10.1101/2020.11.13.381988
Kumar Udit Saumya
1Indian Institute of Technology Mandi, School of Basic Sciences, VPO Kamand, Himachal Pradesh 175005, India
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Kundlik Gadhave
1Indian Institute of Technology Mandi, School of Basic Sciences, VPO Kamand, Himachal Pradesh 175005, India
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Amit Kumar
1Indian Institute of Technology Mandi, School of Basic Sciences, VPO Kamand, Himachal Pradesh 175005, India
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Rajanish Giri
1Indian Institute of Technology Mandi, School of Basic Sciences, VPO Kamand, Himachal Pradesh 175005, India
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  • For correspondence: rajanishgiri@iitmandi.ac.in
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Abstract

Capsid-anchor (CA) of Zika virus (ZIKV) is a small, single-pass transmembrane sequence that separates the capsid (C) protein from downstream pre-membrane (PrM) protein. During ZIKV polyprotein processing, CA is cleaved-off from C and PrM and left as a membrane-embedded peptide. CA plays an essential role in the assembly and maturation of the virus. However, its independent folding behavior is still unknown. Since misfolding and aggregation propensity of transmembrane proteins are now increasingly recognized and has been linked to several proteopathic disorders. Therefore, in this study, we investigated the amyloid-forming propensity of CA at physiological conditions. We observed aggregation behavior of CA peptide using dyebinding assays and ThT kinetics. The morphological analysis of CA aggregates explored by high-resolution microscopy (TEM and AFM) revealed characteristic amyloid-like fibrils. Further, the effect on mammalian cells exhibited the cytotoxic nature of the CA amyloid-fibrils. Our findings collectively shed light on the amyloidogenic phenomenon of flaviviral protein, which may contribute to their infection.

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Schematic representation of Zika virus Capsid anchor forming amyloid aggregates with cytotoxic and hemolytic properties.

Competing Interest Statement

The authors have declared no competing interest.

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Posted November 14, 2020.
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Zika Virus Capsid Anchor Forms Cytotoxic Amyloid-like Fibrils
Kumar Udit Saumya, Kundlik Gadhave, Amit Kumar, Rajanish Giri
bioRxiv 2020.11.13.381988; doi: https://doi.org/10.1101/2020.11.13.381988
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Zika Virus Capsid Anchor Forms Cytotoxic Amyloid-like Fibrils
Kumar Udit Saumya, Kundlik Gadhave, Amit Kumar, Rajanish Giri
bioRxiv 2020.11.13.381988; doi: https://doi.org/10.1101/2020.11.13.381988

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