Structural Motifs and Spatial Structures of Helicase (NS3) and RNA-dependent RNA-polymerase (NS5) of a Flavi-like Kindia tick virus (unclassified Flaviviridae)

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Abstract

Introduction. Kindia tick virus (KITV) is a novel segmented unclassified flavi-like virus of the Flaviviridae family. This virus is associated with ixodes ticks and is potentially pathogenic to humans.

The main goal of this work was to search for structural motifs of viral polypeptides and to develop a 3D-structure for viral proteins of the flavi-like KITV.

Materials and methods. The complete genome sequences for KITV, Zika, dengue, Japanese encephalitis, West Nile and yellow fever viruses were retrieved from GenBank. Bioinformatics analysis was performed using the different software packages.

Results. Analysis of the KITV structural proteins showed that they have no analogues among currently known viral proteins. Spatial models of NS3 and NS5 KITV proteins have been obtained. These models had a high level of topological similarity to the tick-borne encephalitis and dengue viral proteins. The methyltransferase and RNA-dependent RNA-polymerase domains were found in the NS5 KITV. The latter was represented by fingers, palm and thumb subdomains, and motifs A-F. The helicase domain and its main structural motifs I–VI were identified in NS3 KITV. However, the protease domain typical of NS3 flaviviruses was not detected. The highly conserved amino acid motives were detected in the NS3 and NS5 KITV. Also, eight amino acid substitutions characteristic of KITV/2018/1 and KITV/2018/2 were detected, five of them being localized in alpha-helix and three in loops of nonstructural proteins.

Conclusion. Nonstructural proteins of KITV have structural and functional similarities with unsegmented flaviviruses. This confirms their possible evolutionary and taxonomic relationships.

About the authors

A. A. Gladysheva

State Scientific Center of Virology and Biotechnology «Vector»; Novosibirsk National Research State University

Email: gladysheva_aa@vector.nsc.ru
ORCID iD: 0000-0002-9490-1939

Graduate student, Assistant, Department of Molecular Virology for Flaviviruses and Viral Hepatitis

Russian Federation, 630559, Novosibirsk region, Koltsovo; 630090, Novosibirsk

A. V. Gladysheva

State Scientific Center of Virology and Biotechnology «Vector»

Author for correspondence.
Email: gladysheva_av@vector.nsc.ru
ORCID iD: 0000-0002-7396-3954
SPIN-code: 5214-3421
Scopus Author ID: 57194590629

Postgraduate student, Juniour Researcher, Department of Molecular Virology for Flaviviruses and Viral Hepatitis

Russian Federation, 630559, Novosibirsk region, Koltsovo

V. A. Ternovoi

State Scientific Center of Virology and Biotechnology «Vector»

Email: tern@vector.nsc.ru
ORCID iD: 0000-0003-1275-171X

PhD, Leading Researcher, Department of Molecular Virology for Flaviviruses and Viral Hepatitis

Russian Federation, 630559, Novosibirsk region, Koltsovo

V. B. Loktev

State Scientific Center of Virology and Biotechnology «Vector»; Novosibirsk National Research State University

Email: loktev@vector.nsc.ru
ORCID iD: 0000-0002-0229-321X

Dr. Sci. (Biol.), Professor, Head of the Department of Molecular Virology for Flaviviruses and Viral Hepatitis

Russian Federation, 630559, Novosibirsk region, Koltsovo; 630090, Novosibirsk

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2. Fig. 1. Models of spatial organization NS5: a – imposition models of spatial structures NS5: KITV/2018/1 (blue), KITV/2018/2 (green) and dengue virus (red); b – spatial model NS5 KITV/2018/1 with conservative motives A–F; c – imposition of spatial structures NS5 KITV/2018/1 (white/blue) and KITV/2018/2 (gray/green), where detected amino acid substitutions are highlighted in color.

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3. Fig. 2. Alignment of amino acid sequences NS3 (a) and NS5 (b) KITV with flaviviruses. Highly conserved amino acids are highlighted in red; highly conserved amino acids, whose functions are known for flaviviruses, are highlighted with green arrows. Sections of amino acid sequences corresponding to detected motifs are highlighted with colored lines. Elements of secondary structure of viral proteins are indicated for the KITV/2018/1 strain.

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Copyright (c) 2023 Gladysheva A.A., Gladysheva A.V., Ternovoi V.A., Loktev V.B.

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