Analysis of host and viral factors involved in flavivirus symbiosis and evolution

2020 Fiscal Year Final Research Report

• Project Area: Neo-virology: the raison d'etre of viruses
• Project/Area Number: 16H06432
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: MATSUURA Yoshiharu 大阪大学, 微生物病研究所, 教授 (50157252)
• Co-Investigator(Kenkyū-buntansha): 吉住 朋晴 九州大学, 医学研究院, 准教授 (80363373)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: フラビウイルス / 進化 / NS1

Outline of Final Research Achievements

Our previous studies have shown that the binding of ApoE or Erns to the membrane of viral particles is essential for the formation of infectious particles of hepatitis C virus (HCV) and pestiviruses. We have established a system of trans-complementation, and identified the I273H mutation. Although the virus carrying this mutation is capable of replicating the genome, infectious particle formation was inhibited, sugggesting that the NS1 protein is important for virus particle formation. Analysis of the purified NS1 protein with I273 mutation also revealed that this mutation is important for membrane binding. Viruses with this I273 mutation cannot form infectious viral particles, but the exogenous expression of ApoE and Erns compensated for their function. Considering these results, viruses belonging to the Flaviviridae family have a similar mechanism in particle formation. It is possible that viral proteins and host factors have come to be used in the process of evolution.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

本研究は、フラビウイルス内で維持される粒子産生機構に着目し、深く関与する因子を同定したところ、C型肝炎ウイルスではアポリポタンパク質といった宿主因子を利用している一方で、フラビウイルスやぺスチウイルスではウイルスタンパク質であるNS1やErnsを利用していることが明らかになった。このことは進化の過程で宿主因子およびウイルス因子を使い分けるようになったことが予想される。RNAウイルスの新たな進化パターンを明らかにすることができ、この成果は学術的に非常に意義深いと考えられる。