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TMPRSS2-induced Golgi disruption restricts the incorporation of virus envelope glycoproteins into virions

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 disrupted the trans-Golgi by phosphorylating Golgi stacking proteins through ERK activation, which disturbed virion spike incorporation and structural maturation of the viral envelope glycoproteins, causing lower viral infectivity. We found that the 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.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Kosuke Miyauchi

PROVIDER: PXD065094 | JPOST Repository | Wed Apr 15 00:00:00 BST 2026

REPOSITORIES: jPOST

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	20240418_KT_HS_MiyauchiLab_TMPRSS2_whole_1.raw	Raw
	20240418_KT_HS_MiyauchiLab_TMPRSS2_whole_2.raw	Raw
	20240418_KT_HS_MiyauchiLab_TMPRSS2_whole_3.raw	Raw
	20240418_KT_HS_MiyauchiLab_TMPRSS2_whole_4.raw	Raw
	20240418_KT_HS_MiyauchiLab_TMPRSS2_whole_5.raw	Raw

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