イシズ　アヤコ   Ayako Nakamura-Ishizu   石津　綾子    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	総説
言語種別	日本語
査読の有無	査読あり
招待の有無	招待あり
表題	SARS-CoV-2の病態生理
掲載誌名	正式名：東京女子医科大学雑誌 略　 称：東女医大誌 ISSNコード：0040-9022/2432-6178
掲載区分	国内
巻・号・頁	91(1),11-18頁
著者・共著者	中村史雄, 石津綾子
担当区分	責任著者
発行年月	2021/02/25
概要	Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a wide range of clinical manifestations, including acute respiratory distress syndrome, severe inflammation, abnormal blood coagulation, and cytokine storm syndrome. SARS-CoV-2 uniquely facilitates its entry and expan- sion in host cells through the spike protein consisting of S1 (receptor binding domain) and S2 (fusion peptide do- main). The S1 binds to angiotensin-converting enzyme 2 (ACE2), the host cell receptor. The cleavage at the boundary of S1 and S2 by Furin protease and subsequent digestion within the S2 by TMPRSS2 activate the S2 fu- sion peptides, which are necessary for the entry of SARS-CoV-2 into host cells. After infection, SARS-CoV-2 RNA genome encodes viral proteins including structural proteins, RNA polymerases/helicases, and modulators of host- defense system, which inhibit type I-interferon-related immune signaling and signal transducer and activator of transcription 1 (STAT1) signaling. In contrast, SARS-CoV-2 infection activates the proinflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor α (TNFα). In severe cases of COVID-19, these alterations in immune signaling may induce a state of systemic immune dysfunction. Recent studies also revealed the involve- ment of hematopoietic cells and alteration of cellular metabolic state in COVID-19. We here review the patho- genesis of COVID-19, primarily focusing on the molecular mechanism underlying SARS-CoV2 infection and the resulting immunological and hematological alterations.
DOI	10.24488/jtwmu.91.1_11