Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response

By Ilona Glowacka, Stephanie Bertram, M. Müller, P. Allen, E. Soilleux, S. Pfefferle, Imke Steffen, T. Tsegaye, Yuxian He, Kerstin Gnirss and 4 more. Journal of Virology, 2011

974 citations recorded by the source corpus.

Subfields: Epidemiology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/93b1c57024e96675a57072b4299b28082d754f7b

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Citations in the corpus

A decade after SARS: Strategies to control emerging coronaviruses (2013, background): “Post-entry events are dependent on one or more cellular proteases, such as cathepsins, human airway trypsin-like protease (HAT) or transmembrane protease serine 2 (TMPRSS2) 138, 139 , which cleave the spike protein and initiate a variety of conformational changes that are important for membrane fusi”
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor (2020, background): “, 2005) and the serine protease TMPRSS2 (Glowacka et al., 2011; Matsuyama et al., 2010; Shulla et al., 2011) for S protein priming in cell lines, and inhibition of both proteases is required for robust blockade of viral entry (Kawase et al.”
New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? (2020, background): “The virus is then transported into the cell through the early and late endosomes where the host protease cathepsin L further cleaves the S protein at low pH, leading to fusion of the viral envelope and phospholipidic membrane of the endosomes resulting in release of the viral genome into the cell cy”
Host cell proteases: critical determinants of coronavirus tropism and pathogenesis (2014, background): “After TMPRSS2 cleavage, shed fragments of S, including a large 150 kDa fragment, are detected in the supernatant of cells and were shown to act as decoys to anti-S neutralizing antibodies (Glowacka et al., 2011).”
SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far (2020, result): “It has been demonstrated that when the SARS spike protein binds to the ACE-2 receptor ( Figure 3A ), the complex is proteolytically processed by type 2 transmembrane protease TMPRSS2 leading to cleavage of ACE-2 and activation of the spike protein ( Figure 3B ) [21, 22] , similar to the mechanism em”
SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues (2020, positive): “The main host protease that mediates S protein activation on primary target cells and initial viral entry is the Type II transmembrane serine protease TMPRSS2 (Glowacka et al., 2011; Hoffmann et al., 2020; Iwata-Yoshikawa et al., 2019; Matsuyama et al., 2010; Shulla et al., 2011; Walls et al., 2020)”
SARS and MERS: recent insights into emerging coronaviruses (2016, positive): “For example, the spike protein of SARS-CoV is cleaved by cathepsin B and cathepsin L, transmembrane protease serine 2 (TMPRSS2) and possibly other host proteases 130,131 .”
Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein (2012, background): “SARS-CoV S-pseudotyped virions produced in cells expressing TMPRSS2 still rely on endosomal cathepsin for entry, while they are less sensitive to neutralizing antibodies.”
COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses (2020, positive): “The entry mechanism of a coronavirus depends upon cellular proteases which include, human airway trypsin-like protease (HAT), cathepsins and transmembrane protease serine 2 (TMPRSS2) that split the spike protein and establish further penetration changes [28,29].”
Structure, Function, and Evolution of Coronavirus Spike Proteins (2016, background): “Second, in addition to lysosomal proteases, both extracellular proteases (e.g., elastases in the respiratory tract) and cell surface proteases (e.g., TMPRSS2 on the surface of lung cells) also activate SARS-CoV spike for membrane fusion (138–142).”
Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation (2020, background): “6 protease cleavage site that results in an “RRAR” furin recognition site in 2019-nCoV, rather than 82 the single arginine in SARS-CoV (Supplementary Figure 5) (19-22).”