TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein to facilitate cellular entry. Although TMPRSS2 is a well-characterized type II transm...

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Published inViruses Vol. 13; no. 3; p. 384
Main Authors Kishimoto, Mai, Uemura, Kentaro, Sanaki, Takao, Sato, Akihiko, Hall, William W., Kariwa, Hiroaki, Orba, Yasuko, Sawa, Hirofumi, Sasaki, Michihito
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 28.02.2021
MDPI
Subjects
ACE2
Angiotensin
Angiotensin-converting enzyme 2
Angiotensin-Converting Enzyme 2 - metabolism
Animals
Antibodies
Chlorocebus aethiops
Cloning
Communication
Coronaviruses
COVID-19
COVID-19 - metabolism
COVID-19 - virology
Disease transmission
Efficiency
Enzymes
Genes
HEK293 Cells
Humans
Infections
Membrane Proteins - metabolism
Membranes
Pathogenicity
Peptidyl-dipeptidase A
Plasmids
Proteins
Replication
SARS-CoV-2 - metabolism
Serine
Serine Endopeptidases - metabolism
Serine Proteases - metabolism
Serine proteinase
serine proteinases
Severe acute respiratory syndrome coronavirus
Severe acute respiratory syndrome coronavirus 2
severe acute respiratory syndrome-like coronavirus-2 (SARS-CoV-2)
Spike Glycoprotein, Coronavirus - metabolism
Spike protein
tissue tropism
Tropism
type II transmembrane serine protease (TTSP)
Vaccine development
Vero Cells
Virus Internalization
Viruses
United States > US
Japan
Severe acute respiratory syndrome-like coronavirus-2 (SARS-CoV-2)
type II transmembrane serine protease (TTSP)
spike protein
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Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein to facilitate cellular entry. Although TMPRSS2 is a well-characterized type II transmembrane serine protease (TTSP), the role of other TTSPs on the replication of SARS-CoV-2 remains to be elucidated. Here, we have screened 12 TTSPs using human angiotensin-converting enzyme 2-expressing HEK293T (293T-ACE2) cells and Vero E6 cells and demonstrated that exogenous expression of TMPRSS11D and TMPRSS13 enhanced cellular uptake and subsequent replication of SARS-CoV-2. In addition, SARS-CoV-1 and SARS-CoV-2 share the same TTSPs in the viral entry process. Our study demonstrates the impact of host TTSPs on infection of SARS-CoV-2, which may have implications for cell and tissue tropism, for pathogenicity, and potentially for vaccine development.
AbstractList Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein to facilitate cellular entry. Although TMPRSS2 is a well-characterized type II transmembrane serine protease (TTSP), the role of other TTSPs on the replication of SARS-CoV-2 remains to be elucidated. Here, we have screened 12 TTSPs using human angiotensin-converting enzyme 2-expressing HEK293T (293T-ACE2) cells and Vero E6 cells and demonstrated that exogenous expression of TMPRSS11D and TMPRSS13 enhanced cellular uptake and subsequent replication of SARS-CoV-2. In addition, SARS-CoV-1 and SARS-CoV-2 share the same TTSPs in the viral entry process. Our study demonstrates the impact of host TTSPs on infection of SARS-CoV-2, which may have implications for cell and tissue tropism, for pathogenicity, and potentially for vaccine development.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein to facilitate cellular entry. Although TMPRSS2 is a well-characterized type II transmembrane serine protease (TTSP), the role of other TTSPs on the replication of SARS-CoV-2 remains to be elucidated. Here, we have screened 12 TTSPs using human angiotensin-converting enzyme 2-expressing HEK293T (293T-ACE2) cells and Vero E6 cells and demonstrated that exogenous expression of TMPRSS11D and TMPRSS13 enhanced cellular uptake and subsequent replication of SARS-CoV-2. In addition, SARS-CoV-1 and SARS-CoV-2 share the same TTSPs in the viral entry process. Our study demonstrates the impact of host TTSPs on infection of SARS-CoV-2, which may have implications for cell and tissue tropism, for pathogenicity, and potentially for vaccine development.Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein to facilitate cellular entry. Although TMPRSS2 is a well-characterized type II transmembrane serine protease (TTSP), the role of other TTSPs on the replication of SARS-CoV-2 remains to be elucidated. Here, we have screened 12 TTSPs using human angiotensin-converting enzyme 2-expressing HEK293T (293T-ACE2) cells and Vero E6 cells and demonstrated that exogenous expression of TMPRSS11D and TMPRSS13 enhanced cellular uptake and subsequent replication of SARS-CoV-2. In addition, SARS-CoV-1 and SARS-CoV-2 share the same TTSPs in the viral entry process. Our study demonstrates the impact of host TTSPs on infection of SARS-CoV-2, which may have implications for cell and tissue tropism, for pathogenicity, and potentially for vaccine development.
Author Kishimoto, Mai
Sato, Akihiko
Orba, Yasuko
Uemura, Kentaro
Sanaki, Takao
Sawa, Hirofumi
Kariwa, Hiroaki
Hall, William W.
Sasaki, Michihito
AuthorAffiliation 6 Centre for Research in Infectious Diseases, School of Medicine, University College Dublin, DO4V1W8 Dublin, Ireland
4 Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, Sapporo 060-0812, Japan
3 Division of Anti-Virus Drug Research, Research Center for Zoonosis Control, Hokkaido University, N20 W10, Kita-ku, Sapporo 001-0020, Japan
8 Global Virus Network, 725 West Lombard St, Room S413, Baltimore, MD 21201, USA
7 International Collaboration Unit, Research Center for Zoonosis Control, Hokkaido University, N20 W10, Kita-ku, Sapporo 001-0020, Japan
9 Laboratory of Public Health, Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan; kariwa@vetmed.hokudai.ac.jp
5 National Virus Reference Laboratory, School of Medicine, University College Dublin, DO4V1W8 Dublin, Ireland; william.hall@ucd.ie
2 Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-
AuthorAffiliation_xml – name: 2 Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan; kentaro.uemura@shionogi.co.jp (K.U.); takao.sanaki@shionogi.co.jp (T.S.); akihiko.sato@shionogi.co.jp (A.S.)
– name: 1 Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, N20 W10, Kita-ku, Sapporo 001-0020, Japan; kishimoto@czc.hokudai.ac.jp (M.K.); orbay@czc.hokudai.ac.jp (Y.O.); h-sawa@czc.hokudai.ac.jp (H.S.)
– name: 7 International Collaboration Unit, Research Center for Zoonosis Control, Hokkaido University, N20 W10, Kita-ku, Sapporo 001-0020, Japan
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– name: 6 Centre for Research in Infectious Diseases, School of Medicine, University College Dublin, DO4V1W8 Dublin, Ireland
– name: 8 Global Virus Network, 725 West Lombard St, Room S413, Baltimore, MD 21201, USA
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Keywords Severe acute respiratory syndrome-like coronavirus-2 (SARS-CoV-2)
type II transmembrane serine protease (TTSP)
spike protein
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Snippet Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2...
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StartPage 384
SubjectTerms ACE2
Angiotensin
Angiotensin-converting enzyme 2
Angiotensin-Converting Enzyme 2 - metabolism
Animals
Antibodies
Chlorocebus aethiops
Cloning
Communication
Coronaviruses
COVID-19
COVID-19 - metabolism
COVID-19 - virology
Disease transmission
Efficiency
Enzymes
Genes
HEK293 Cells
Humans
Infections
Membrane Proteins - metabolism
Membranes
Pathogenicity
Peptidyl-dipeptidase A
Plasmids
Proteins
Replication
SARS-CoV-2 - metabolism
Serine
Serine Endopeptidases - metabolism
Serine Proteases - metabolism
Serine proteinase
serine proteinases
Severe acute respiratory syndrome coronavirus
Severe acute respiratory syndrome coronavirus 2
severe acute respiratory syndrome-like coronavirus-2 (SARS-CoV-2)
Spike Glycoprotein, Coronavirus - metabolism
Spike protein
tissue tropism
Tropism
type II transmembrane serine protease (TTSP)
Vaccine development
Vero Cells
Virus Internalization
Viruses
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Title TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein
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