Intestinal innate immune response to enterically transmitted hepatitis virus
| Project/Area Number |
18K05987
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 42020:Veterinary medical science-related
|
|---|
| Research Institution | National Institute of Infectious Diseases |
|---|
Principal Investigator |
Hirai-Yuki Asuka 国立感染症研究所, 安全実験管理部, 主任研究官 (50450557)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
山根 大典 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (60782761)
|
|---|
| Project Period (FY) |
2018-04-01 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | A型肝炎 / マウスモデル / 経口感染 / A型肝炎ウイルス / I・III型IFN受容体遺伝子欠損マウス / 肝炎ウイルス / 自然免疫 / 腸管 / III型IFN |
|---|
| Outline of Final Research Achievements |
In this study, we have developed a novel murine model of hepatitis A virus (HAV) infection that recapitulates critical features of type A hepatitis in humans. Most importantly, the mice can be infected via oral route which is the natural route of this fecal-oral transmitted virus. Previous studies have relied on new world monkeys which are permissive for oral infection of HAV, to investigate pathogenesis to orally transmitted hepatitis virus. This murine model thus offers an excellent platform for research and development of inhibitors for oral viral infections. Further studies are necessary to elucidate the molecular mechanisms by which this hepatotropic virus over comes intestinal barrier without replicating in the epithelium, get into bloodstream and reach the target organ. This could be applicable to other oral viral infections and may provide a basis for developing effective prophylaxis.
|
| Academic Significance and Societal Importance of the Research Achievements |
HAVが腸管上皮で初期増殖しないことは予想外であったが、今後このマウスモデルを用いて、腸管組織に感染しないウイルスが腸管から血中そして標的臓器へ到達するメカニズムを明らかにすることは、新たな感染予防法の開発に繋がる。また、このマウスモデルを用いて研究開発を行うことは、国際的な動物実験倫理原則「3R」の一つである「Replacement」の観点から、サル類から系統発生的に下位な動物種への代替の成功例としても評価され、社会的意義は大きい。
|
Report
(6 results)
Research Products
(7 results)
-
-
[Journal Article] Macrophage depletion reactivates fecal virus shedding following resolution of acute hepatitis A in Ifnar1-/- mice.2022
Author(s)
Shiota T, Matsuda M, Zheng X, Nagata N, Ishii K, Suzuki R, Muramatsu M, Takimoto K, Hanaki K, Lemon SM, McGivern D, Hirai-Yuki A
-
Journal Title
Journal of Virology
Volume: 96
Issue: 23
Pages: 1-14
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Basal expression of interferon regulatory factor 1 drives intrinsic hepatocyte resistance to multiple RNA viruses2019
Author(s)
Yamane D, Feng H, Rivera-Serrano EE, Selitsky SR, Hirai-Yuki A, Das A, McKnight KL, Misumi I, Hensley L, Lovell W, González-López O, Suzuki R, Matsuda M, Nakanishi H, Ohto-Nakanishi T, Hishiki T, Wauthier E, Oikawa T, Morita K, Reid LM, Sethupathy P, Kohara M, Whitmire JK, Lemon SM
-
Journal Title
Nature Microbiology
Volume: 印刷中
Issue: 7
Pages: 1096-1104
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
