Investigation for pathogenesis of influenza virus and SARS coronavirus
| Project/Area Number |
17591053
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
膠原病・アレルギー・感染症内科学
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
NAKAYA Takaaki Osaka University, Research Institute for Microbial Diseases, Associated Professor (80271633)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HAGIWARA Katsuro Rakuno University, 獣医学部, Associated Professor (50295896)
SHIME Nobuaki Kyoto Prefectural University of Medicine, 医学研究科, Assistant Professor (00260795)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | influenza virus / SARS coronavirus / Newcastle disease virus / Recombinant virus / ニューカッスル病ウイルス / 重症急性呼吸器症候群 / リバースジェネティックス / シュードウイルス / RNAレプリコン |
|---|
| Research Abstract |
The unprecedented re-emergence of highly pathogenic avian influenza H5N1 viruses (H5N1-Flu) and the outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV) pose a significant threat to humans. Better basic knowledge of these highly pathogenic viruses and novel technologies such as reverse genetics will help us to generate effective prophylactic and/or therapeutic strategies to control the disease load. We have developed the reverse genetics of negative strand RNA viruses and were analyzing the mechanisms behind the replication and cytopathicity of these viruses.
Primary airway epithelial cells from alveolar tissues were prepared from 1-year-old pigs and the growth kinetics of avian H5 influenza viruses in these cells was investigated. H5N1 virus significantly induced cell death, especially apoptosis, in porcine airway epithelial cells although these three viruses induced similar cell toxicity in chicken embryonic fibroblasts, suggesting that avian H5N1 influenza virus leads
… More
severe cell death in mammalian airway epithelial cells due to the induction of apoptosis.
A cell clone #21 is a long-term producer of the infectious SARS-CoV, although the incorporation rate of spike (S) protein into virions is significantly lower. Sequencing analysis of the viral structural proteins revealed four and one amino acid substitutions in the S and membrane (M) proteins, respectively. We demonstrated, using a viral-like particle formation system, that the S mutations were involved in lower incorporation of the S protein into virions, although the M mutation disrupting the glycosylation was not involved in this phenotype. Further mutational experiments identified two substitutions, Y442C and L472F, within the receptor binding domain that could be critical for the reduced S incorporation, as well as reduced binding affinity between the S and ACE2 receptor. Thus, these two amino acid substitutions might lead to a conformational change in the S protein, resulting in reduced incorporation into viral particles. Less
|
Report
(3 results)
Research Products
(12 results)
-
-
-
-
-
-
-
[Journal Article] Cytokine genetic ajuvant facilitates prophylactic intravascular DNA vaccine against acute and latent herpes simplex virus infection in mice.2005
Author(s)
F-D Cui, H Asada, M-L Jin, T Kishida, M Shin-Ya, T Nakaya, M Kita, M Ishii, M Iwai, T Okanoue, J Imanishi, O Mazda
-
Journal Title
Gene Therapy 12
Pages: 160-168
Related Report
-
-
-
-
-
