TY - JOUR

T1 - Structural Motifs and Spatial Structures of Helicase (NS3) and RNA-dependent RNA-polymerase (NS5) of a Flavi-like Kindia tick virus (unclassified Flaviviridae)

AU - Gladysheva, Anastasia A.

AU - Gladysheva, Anastasia V.

AU - Ternovoi, Vladimir A.

AU - Loktev, Valery B.

N1 - The study was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement No. 075-15-2021-1355 dated October 12, 2021) as a part of the implementation of certain activities of the Federal Scientific and Technical Program for the Development of Synchrotron and Neutron Research and Research Infrastructure for 2019–2027.

PY - 2023/3/11

Y1 - 2023/3/11

N2 - 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.

AB - 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.

KW - AlphaFold2

KW - Flaviviridae

KW - Jingmen tick viruses

KW - Kindia tick virus

KW - segmented flavi-like viruses

KW - spatial models

KW - viral proteins

KW - Humans

KW - Animals

KW - Ticks/genetics

KW - RNA-Dependent RNA Polymerase/metabolism

KW - Viral Nonstructural Proteins/genetics

KW - Guinea

KW - Flaviviridae/genetics

KW - Zika Virus/genetics

KW - Dengue

KW - RNA

KW - Zika Virus Infection

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85151044979&origin=inward&txGid=9de353010ad63f8ed775619a5834f9e8

UR - https://www.mendeley.com/catalogue/484a4e8b-83f9-3692-9e2c-b8ea15345c45/

U2 - 10.36233/0507-4088-142

DO - 10.36233/0507-4088-142

M3 - Article

C2 - 36961231

VL - 68

SP - 7

EP - 17

JO - Вопросы вирусологии

JF - Вопросы вирусологии

SN - 0507-4088

IS - 1

ER -