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10.1128/mbio.03600-21 http://scihub22266oqcxt.onion/10.1128/mbio.03600-21 35100869!8805026!35100869     free     free     free Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       mBio 2021 ; 13 (1): e0360021 Nephropedia Template TP {{tp|p=35100869|t=2021. Gasdermin D Inhibits Coronavirus Infection by Promoting the Noncanonical Secretion of Beta Interferon |pdf=|usr=}}{{35100869}} gab.com Text Gasdermin D Inhibits Coronavirus Infection by Promoting the Noncanonical Secretion of Beta Interferon JO: mBio http://www.kidney.de/pget.php?&tw=1&pmid=35100869 #FOAvip Pyroptosis, a programmed cell death, functions as an innate immune effector mechanism and plays a crucial role against microbial invasion. Gasdermin D (GSDMD), as the main pyroptosis effector, mediates pyroptosis and promotes releasing proinflammatory molecules into the extracellular environment through pore-forming activity, modifying inflammation and immune responses. While the substantial importance of GSDMD in microbial infection and cancer has been widely investigated, the role of GSDMD in virus infection, including coronaviruses, remains unclear. Enteric coronavirus transmissible gastroenteritis virus (TGEV) and porcine deltacoronavirus (PDCoV) are the major agents for lethal watery diarrhea in neonatal pigs and pose the potential for spillover from pigs to humans. In this study, we found that alphacoronavirus TGEV upregulated and activated GSDMD, resulting in pyroptosis after infection. Furthermore, the fragment of swine GSDMD from amino acids 242 to 279 (242-279 fragment) was required to induce pyroptosis. Notably, GSDMD strongly inhibited both TGEV and PDCoV infection. Mechanistically, the antiviral activity of GSDMD was mediated through promoting the nonclassical release of antiviral beta interferon (IFN-beta) and then enhancing the interferon-stimulated gene (ISG) responses. These findings showed that GSDMD dampens coronavirus infection by an uncovered GSDMD-mediated IFN secretion, which may present a novel target of coronavirus antiviral therapeutics. IMPORTANCE Coronaviruses, primarily targeting respiratory and gastrointestinal epithelia in vivo, have a serious impact on humans and animals. GSDMD, a main executioner of pyroptosis, is highly expressed in epithelial cells and involves viral infection pathogenesis. While the functions and importance of GSDMD as a critical regulator of inflammasome activities in response to intracellular bacterial infection have been extensively investigated, the roles of GSDMD during coronavirus infection remain unclear. We here show that alphacoronavirus TGEV triggered pyroptosis and upregulated GSDMD expression, while GSDMD broadly suppressed the infection of enteric coronavirus TGEV and PDCoV by its pore-forming activity via promoting unconventional release of IFN-beta. Our study highlights the importance of GSDMD as a regulator of innate immunity and may open new avenues for treating coronavirus infection. Twit Text FOAVip Gasdermin D Inhibits Coronavirus Infection by Promoting the Noncanonical Secretion of Beta Interferon ????mBio http://www.kidney.de/pget.php?&tw=1&pmid=35100869 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=35100869 #FOAvip English Wikipedia <ref>{{Cite pmid|35100869}}</ref> Gasdermin D Inhibits Coronavirus Infection by Promoting the Noncanonical Secretion of Beta Interferon #MMPMID35100869 Zhao L; Li L; Xue M; Liu X; Jiang C; Wang W; Tang L; Feng L; Liu P mBio 2021[Feb]; 13 (1): e0360021 PMID35100869show ga Pyroptosis, a programmed cell death, functions as an innate immune effector mechanism and plays a crucial role against microbial invasion. Gasdermin D (GSDMD), as the main pyroptosis effector, mediates pyroptosis and promotes releasing proinflammatory molecules into the extracellular environment through pore-forming activity, modifying inflammation and immune responses. While the substantial importance of GSDMD in microbial infection and cancer has been widely investigated, the role of GSDMD in virus infection, including coronaviruses, remains unclear. Enteric coronavirus transmissible gastroenteritis virus (TGEV) and porcine deltacoronavirus (PDCoV) are the major agents for lethal watery diarrhea in neonatal pigs and pose the potential for spillover from pigs to humans. In this study, we found that alphacoronavirus TGEV upregulated and activated GSDMD, resulting in pyroptosis after infection. Furthermore, the fragment of swine GSDMD from amino acids 242 to 279 (242-279 fragment) was required to induce pyroptosis. Notably, GSDMD strongly inhibited both TGEV and PDCoV infection. Mechanistically, the antiviral activity of GSDMD was mediated through promoting the nonclassical release of antiviral beta interferon (IFN-beta) and then enhancing the interferon-stimulated gene (ISG) responses. These findings showed that GSDMD dampens coronavirus infection by an uncovered GSDMD-mediated IFN secretion, which may present a novel target of coronavirus antiviral therapeutics. IMPORTANCE Coronaviruses, primarily targeting respiratory and gastrointestinal epithelia in vivo, have a serious impact on humans and animals. GSDMD, a main executioner of pyroptosis, is highly expressed in epithelial cells and involves viral infection pathogenesis. While the functions and importance of GSDMD as a critical regulator of inflammasome activities in response to intracellular bacterial infection have been extensively investigated, the roles of GSDMD during coronavirus infection remain unclear. We here show that alphacoronavirus TGEV triggered pyroptosis and upregulated GSDMD expression, while GSDMD broadly suppressed the infection of enteric coronavirus TGEV and PDCoV by its pore-forming activity via promoting unconventional release of IFN-beta. Our study highlights the importance of GSDMD as a regulator of innate immunity and may open new avenues for treating coronavirus infection. |*Coronavirus[MESH] |*Coronavirus Infections[MESH] |*Transmissible gastroenteritis virus/genetics/metabolism[MESH] |Animals[MESH] |Antiviral Agents/metabolism[MESH] |Gasdermins[MESH] |Humans[MESH] |Interferon-beta/metabolism[MESH]Gasdermin D Inhibits Coronavirus Infection by Promoting the Noncanonic(epmc).pdf DeepDyve Pubget Overpricing