| Project/Area Number |
16017308
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
TAGUCHI Fumihiro National Institute of Infectious Diseases (NIID), Virology III, Laboratory chief, 室長 (30107429)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUYAMA Shutoku NIID, Virology III, Research associate, 研究員
MORIKAWA Shigeru NIID, Virology I, Laboratory chief, 室長 (00167686)
UJIKE Makoto NIID, Virology III, Research associate, 研究員
SHIRATO Kenya NIID, Virology III, Research associate, 研究員
座本 綾 国立感染症研究所, 動物管理室, 研究員 (10392325)
渡辺 理恵 国立感染症研究所, ウイルス第三部, リサーチレジデント
中垣 慶子 国立感染症研究所, ウイルス第三部, 臨時職員
水谷 哲也 国立感染症研究所, ウイルス第1部, 主任研究官 (70281681)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 2004: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | coronaviruses / SARS-CoV / MHV / spike (S) protein / cell entry / protease / receptor / ウイルスレセプター / スパイク(S)蛋白 / プロテアーセ / S蛋白 / プロテアーゼ / レセプター / エンドゾーム |
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| Research Abstract |
1) Research on SARS coronavirus (SARS-CoV) infection :
It was reported that SARS-CoV enters into cells via endosomal pathway. We found that SARS-CoV also enters cells directly from cell surface, when cell-attached viruses are treated with proteases, such as trypsin or elastase that induces. S protein cleavage as well as fusion activity. Virus entry from plasma membrane was revealed to result in a 100 to 1000 more efficient infection than the infection via endosomal pathway. This could suggest that high replication of SARS-CoV in the lung or intestine, the major target organs of SARS, is attributed to the proteases produced in those organs. This protease-mediated enhancement of SARS-CoV infection could explain how severe respiratory disease is produced by SARS-CoV infection, even if this virus is allowed to grow in a variety of organs that express its receptor ACE2. Studies are in progress whether such proteases produced in mice induce severe respiratory disease or not.
2) Research on murine coronavirus mouse hepatitis virus (MHV) infection :
Highly neurotropic MHV, JIEVIV, spreads from cells infected via its receptor (CEACAM1) to CEACAM1-negative BHK cells (called receptor-independent infection). We have shown that JHMV virion can directly infect BHK by spinoculation (virus inoculated cells as well as inoculated viruses were spun at 3000 rpm for 2 h), indicating that JHMV virion has a unique feature for infection. It was further shown that this feature is dependent upon its S protein, which is activated for fusion by a naturally occurring manner, without binding to its specific receptor.
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