2004 Fiscal Year Final Research Report Summary
Role of neuraminidase in the initial stage of influenza virus infection.
| Project/Area Number |
15590425
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
OHUCH Masanobu Kawasaki Medical School, Faculty of Medicine, Professor, 医学部, 教授 (80107185)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Tatsuya Kawasaki Medical School, Faculty of Medicine, Research Assistant, 医学部, 助手 (00309543)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Neuraminidase / Influenza virus / Initial stage of infection / Inhibitor / Receptor / Binding efficiency / Endocytosis |
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| Research Abstract |
Influenza virus has hemagglutinin (HA) and neuraminidase (NA) spikes. By the action of HA, the virus binds to cellular sialoglycans (virus receptor) and enters the target cell. NA is thought to release progeny virus propagated in the cell by digesting sialoglycans on the virus and infected cell. Thus, it is generally though that HA works in the initial stage and NA works in the final stage of viral infection. We think, however, NA should work also in the initial stage, that is, virus adsorption and penetration to the target cell, and studied this subject. The following results were obtained.
1.When influenza A/Aichi/68(H3N2) virus infected to MDCK (derived from canine kidney) and A549 (derived from human lung carcinoma) cells in the presence of NA inhibitor, the infection efficiency was reduced by 1/4 - 1/10. The reduction was achieved within 1 h incubation with the inhibitor.
2.The initial stage of infection could be divided into three steps, 1)virus binding to receptor, 2)virus entry through cellular endocytosis, 3)membrane fusion of virus and endsome. When the virus binding was assessed by hemagglutination test, the titer showed twice higher under the conditions in which NA worked. It suggested that NA might promote the virus binding to receptor. When the membrane fusion was assessed by hemolysis test, the activity was reduced to 1 /2 in the presence of NA inhibitor. This might be explained with the reduced virus binding. These results indicated that 2) step, the virus entry through endocytosis, should be dominantly affected by NA inhibitor, rather than steps of 1) and 3).
To infect cell, the virus must bind to an endocytosis-active region. When the virus binds to inappropriate regions, it can move to other places by the NA action. Thus, NA may enhance the infection efficiency.
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