Annotation of HAZV segmented genome internal region necessary for viral propagation

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22770
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Nagasaki University (2021); Wakayama Medical University (2020)
• Principal Investigator: YAMAGATA Yutaro 長崎大学, 熱帯医学研究所, 特任研究員 (70879410)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: ウイルス学 / ハザラウイルス / ミニゲノム / 転写 / 複製 / 膜蛋白質

Outline of Final Research Achievements

Hazaravirus segmental genome regions required for transcriptional replication and packaging into viral particles were explored using a minigenome system, and it was found that in M-segment untranslational region, 81-162 nucleotides from the end of 5'-terminal may contain the region important for transcriptional replication. The translational region was also explored, but no sequences with increased minigenomic activity were found. Since some of the design and reproducibility of the experimental system created by the predecessor were found to be problematic, improvement of the experimental system was proceeded by examining the conditions and constructing a VLP and reverse genetics system. In addition, cell lines that constantly express Hazaravirus G protein were established, and analysis of mutations in candidate cleavage sites of G prorein resulted that the location of the most common G protein cleavage site is in the vicinity of the RRTN site.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

クリミアコンゴ出血熱ウイルス(CCHFV)は重篤な出血熱症状を引き起こし高い致死率を有する病原性ウイルスであり、有効な治療手段の確立が求められている。ハザラウイルス(HAZV)は、CCHFVに遺伝学的に近縁だがヒトに病原性を示さないため、CCHFVのモデルウイルスとして研究に用いられる。本研究の成果はHAZVの増殖に重要な要因の探索の途中段階にとどまり、HAZVの具体的な増殖機構の解明にまで踏み込む成果は得られなかったが、さらに研究を進めHAZVの増殖機構を解明することで、近縁種であるCCHFVの詳細な増殖機構を解明し、CCHFの有効な治療手段を確立する手掛かりを得られることが期待される。