2021 Fiscal Year Final Research Report
Analysis of the role of intestinal bacteria in hepatitis caused by murine herpesvirus 68 primary infection in mice.
| Project/Area Number |
19K07577
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 49060:Virology-related
|
|---|
| Research Institution | Tottori University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | Epstein-Barr virus / Herpesvirus / Infectous mononucleosis / Murine herpesvirus 68 |
|---|
| Outline of Final Research Achievements |
EB virus causes infectious mononucleosis (IM) with hepatitis in primary infected adults, but the mechanism of pathogenesis is not well understood. We have previously shown that intestinal bacterial products may be associated with the hepatitis using MHV68-infected mice. In the present study, we evaluated the impact of lypopolysaccaride (LPS) and peptideglycan (PDG) as candidates of intestinal bacterial products. As the result, Neutralizing antibodies to TLR4, LPS receptor, suppressed hepatitis. However, neutralizing antibodies to TLR2, PDG receptor, did not inhibit. Furthermore, the TLR4 inhibitor C34 suppressed hepatitis. These results suggest that the LPS-TLR4 pathway may be associated with the hepatitis in IM.
|
| Free Research Field |
ウイルス学
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究はこれまで未知であったEBV肝炎の発症機構において，腸内細菌由来産物であるLPSによるTLR4を介したシグナル誘導がEBV肝炎の発症に関与している可能性を初めて示した．LPSは主にグラム陰性菌の細胞壁に由来するため、腸内細菌叢におけるグラム陰性菌の寄与が強く示唆され、腸内細菌叢を制御することでEBV肝炎を予防できる可能性が示された．また，TLR4阻害剤C34がMHV68感染マウスに生じる肝炎を抑制したことから，TLR4阻害剤を用いることでEBV肝炎が治療できる可能性を初めて示した．本研究で得られた知見はEBV肝炎の予防法や治療法の開発につながる可能性を示す．
|
