Identification and epidemiological study of an uncultured flavivirus from ticks using viral metagenomics and pseudoinfectious viral particles

• 成果类型: Article
• 署名作者: Kobayashi, Daisuke; Inoue, Yusuke; Suzuki, Ryosuke; Matsuda, Mami; Shimoda, Hiroshi; Faizah, Astri Nur; Kaku, Yoshihiro; Ishijima, Keita; Kuroda, Yudai; Tatemoto, Kango; Mendoza, Milagros Virhuez-; Harada, Michiko; Nishino, Ayano; Inumaru, Mizue; Yonemitsu, Kenzo; Kuwata, Ryusei; Takano, Ai; Watanabe, Mamoru; Higa, Yukiko; Sawabe, Kyoko; Maeda, Ken; Isawa, Haruhiko
• 署名单位: Japan Institute for Health Security (JIHS); National Institute of Infectious Diseases (NIID); Japan Institute for Health Security (JIHS); National Institute of Infectious Diseases (NIID); Japan Institute for Health Security (JIHS); National Institute of Infectious Diseases (NIID); Yamaguchi University; Japan Institute for Health Security (JIHS); National Institute of Infectious Diseases (NIID); Okayama University of Science
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14195
• DOI: 10.1073/pnas.2319400121
• 发表日期: 2024-05-07
• 关键词: japanese encephalitis-virus; arthropod-borne viruses; genetic-characterization; wild boars; host-range; DISCOVERY; antibody; viremia; transmission; phlebovirus

摘要

During their blood - feeding process, ticks are known to transmit various viruses to vertebrates, including humans. Recent viral metagenomic analyses using nextgeneration sequencing (NGS) have revealed that blood - feeding arthropods like ticks harbor a large diversity of viruses. However, many of these viruses have not been isolated or cultured, and their basic characteristics remain unknown. This study aimed to present the identification of a difficult - to - culture virus in ticks using NGS and to understand its epidemic dynamics using molecular biology techniques. During routine tick - borne virus surveillance in Japan, an unknown flaviviral sequence was detected via virome analysis of host - questing ticks. Similar viral sequences have been detected in the sera of sika deer and wild boars in Japan, and this virus was tentatively named the Saruyama virus (SAYAV). Because SAYAV did not propagate in any cultured cells tested, singleround infectious virus particles (SRIP) were generated based on its structural protein gene sequence utilizing a yellow fever virus - based replicon system to understand its nationwide endemic status. Seroepidemiological studies using SRIP as antigens have demonstrated the presence of neutralizing antibodies against SAYAV in sika deer and wild boar captured at several locations in Japan, suggesting that SAYAV is endemic throughout Japan. Phylogenetic analyses have revealed that SAYAV forms a sister clade with the Orthoflavivirus genus, which includes important mosquito - and tick - borne pathogenic viruses. This shows that SAYAV evolved into a lineage independent of the known orthoflaviviruses. This study demonstrates a unique approach for understanding the epidemiology of uncultured viruses by combining viral metagenomics and pseudoinfectious viral particles.