RRC ID 88479
著者 Seki S, Harada S, Sugimoto-Ishige A, Unno M, Sakuma M, Ito S, Yamamoto H, Tanabe A, Matsuoka S, Makino-Okamura C, Ki S, Fukuyama H, Harada M, Tsumagari K, Imami K, Saito T, Kubo M, Suzuki T, Koseki H, Matano T, Miyauchi K.
タイトル TMPRSS2-induced Golgi disruption restricts the incorporation of virus envelope glycoproteins into virions.
ジャーナル EMBO Rep
Abstract Understanding the relationship between viral proteins and host factors is essential for developing strategies to control virus infections. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells using angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as viral receptor and priming protease during the viral entry phase. Here, we report that TMPRSS2 reduces the infectivity of SARS-CoV-2 and HIV-1 during the viral production phase. Treatment of virus-producing cells with a TMPRSS2 inhibitor increases the production of infectious virions. TMPRSS2 enzymatic activity specifically disrupts the trans-Golgi by phosphorylating Golgi stacking proteins through ERK activation, which disturbs virion spike incorporation and structural maturation of the viral envelope glycoproteins, causing lower viral infectivity. We find that SARS-CoV-2 envelope protein (E protein) counteracts this TMPRSS2 activity to rescue SARS-CoV-2-S incorporation. These results demonstrate negative regulation of viral envelope glycoprotein incorporation by TMPRSS2 and reveal that SARS-CoV-2 regulates the Golgi system to create an optimal viral replication environment.
公開日 2026-5-19
DOI 10.1038/s44319-026-00797-2
PII 10.1038/s44319-026-00797-2
PMID 42156913
リソース情報
ヒト・動物細胞 Jurkat(RCB3052) CACO-2(RCB0988) COS-1(RCB0143)