Ubiquitin accumulation induced by the finger and palm sub-domains of NS5 modulates the replication of West Nile virus

Shintaro Kobayashi; Ryoko Kawakami; Chisaki Takeda; Keisuke Maezono; Passawat Thammahakin; Haruto Eguchi; Bernard M Hang'ombe; Yasuko Orba; Hirofumi Sawa; Kentaro Yoshii; Hiroaki Kariwa

doi:10.1016/j.virol.2023.109902

Ubiquitin accumulation induced by the finger and palm sub-domains of NS5 modulates the replication of West Nile virus

Virology. 2023 Nov:588:109902. doi: 10.1016/j.virol.2023.109902. Epub 2023 Oct 12.

Affiliations

¹ Laboratory of Public Health, Hokkaido University, N18, W9, Kita-ku, Sapporo, 060-0818, Japan; Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Hokkaido, Japan. Electronic address: shin-kobayashi@vetmed.hokudai.ac.jp.
² Laboratory of Public Health, Hokkaido University, N18, W9, Kita-ku, Sapporo, 060-0818, Japan.
³ Department of Para-Clinical Studies, School of Veterinary Medicine, The University of Zambia, P.O. Box 32379, Lusaka, 10101, Zambia; Africa Center of Excellence for Infectious Diseases of Humans and Animals, The University of Zambia, P.O. Box 32379, Lusaka, 10101, Zambia.
⁴ Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Hokkaido, Japan; Division of Molecular Pathobiology, International Institute for Zoonosis Control, N20, W10, Kita-ku, Sapporo, 001-0020, Japan; One Health Research Center, Hokkaido University, Hokkaido, Japan; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Hokkaido, Japan.
⁵ Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Hokkaido, Japan; Division of Molecular Pathobiology, International Institute for Zoonosis Control, N20, W10, Kita-ku, Sapporo, 001-0020, Japan; One Health Research Center, Hokkaido University, Hokkaido, Japan; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Hokkaido, Japan; Global Virus Network, Baltimore, MD, USA.
⁶ Laboratory of Public Health, Hokkaido University, N18, W9, Kita-ku, Sapporo, 060-0818, Japan; National Research Center for the Control and Prevention of Infectious diseases (CCPID), Nagasaki University, Nagasaki, Japan.

PMID: 37856911
DOI: 10.1016/j.virol.2023.109902

Abstract

West Nile virus (WNV) causes encephalitis in human and animals. WNV is phylogenetically classified into at least five distinct genetic lineages with different pathogenicity. The pathogenesis of West Nile encephalitis is affected by ubiquitin accumulation in infected cells, but the mechanism is unknown. In this study, the association between ubiquitin accumulation and WNV pathogenicity was investigated. Ubiquitin accumulation was detected in cells infected with NY99 strain belonging to lineage-1, but not FCG and Zmq16 strains belonging to lineage-2. Substitution of the Finger and Palm sub-domains of NS5 from lineage-1 to -2 decreased ubiquitin accumulation and viral replication. Furthermore, the survival rate was increased, and viral replication and ubiquitin accumulation in the brain were attenuated, in mice inoculated with the substituted WNV compared with lineage-1 WNV. Therefore, the intracellular ubiquitin accumulation induced by the Finger and Palm sub-domains of NS5 is linked to the differences in pathogenicity among WNV lineages.

Keywords: Encephalitis; NS5; Ubiquitin accumulation; Viral replication; West Nile virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain
Humans
Mice
Ubiquitin
Virus Replication / genetics
West Nile Fever*
West Nile virus* / genetics

Substances

Ubiquitin