2021 Fiscal Year Final Research Report
Structure analysis of human herpesvirus 6 glycoprotein complex which is essential for the receptor binding
| Project/Area Number |
19K06512
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 43020:Structural biochemistry-related
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | ヒトヘルペスウイルス6 / X線結晶構造解析 |
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| Outline of Final Research Achievements |
Human herpesvirus 6 (HHV-6) has a glycoprotein complex gH/gL/gQ1/gQ2 on the virion surface, and the complex plays an essential role on recognizing the host receptor CD134. The interaction between gH/gL/gQ1/gQ2 and CD134 is important for the infection, and hence the inhibition by antibodies results in neutralization. In this study the structure of gH/gL/gQ1/gQ2 and its interaction with CD134 or antibodies were analyzed. The affinity between gH/gL/gQ1/gQ2 and CD134 was revealed to be high enough to sense target cells. Inhibition of the molecular interaction by a neutralizing antibody was demonstrated. The overall shape of gH/gL/gQ1/gQ2 was visualized by electron microscopy, and biding locations of two neutralizing antibodies on the gH/gL/gQ1/gQ2 were also revealed. Protein crystals of gH/gL/gQ1/gQ2 with Fabs of neutralizing antibodies were obtained. X-ray diffraction measurement using the crystals resulted in a diffraction data at the maximum resolution 3.8 angstrom.
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| Free Research Field |
構造生物学
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトヘルペスウイルス6は全てのヒトが乳幼児期に感染するウイルスであり、生涯にわたり体内に潜伏感染し続けている病原体である。初感染時や再活性化時に脳炎を引き起こし得る危険性が知られており、未だ効果的な対処法は確立されていない。感染にはgH/gL/gQ1/gQ2と呼ばれる因子が必須の働きを担っているが、その立体構造や機能については未だに不明な点が多く残されている。本研究ではgH/gL/gQ1/gQ2の分子としての立体構造を解析するとともに、感染標的となる細胞で受容体となっているタンパク質との相互作用や、免疫系が作り出す中和抗体との相互作用の解析を行うことで、その機能についての知見を得た。
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