Citations 2
Ebola virus matrix protein VP40 triggers inflammatory responses linked to the ebolavirus virulence
Yamaoka, Satoko , Mhamdi, Zeineb, Wang, Lin , Swenson, Vaille A. , McNally, Kristin L., Lu, Shao‐Chia , Singh, Reema , Saundh, Stephanie L. , Zell, Brady N. , Best, Sonja M. , Barry, Michael A , Ebihara, Hideki , Yamaoka, Satoko , Zell, Brady , Wang, Lin , Barry, Michael A. , Rasmussen, Angela L , Ebihara, Hideki
Proceedings of the National Academy of Sciences | December 29, 2025 | Volume: 123 | Issue: 1 | Pages: No page available
Uncontrolled systemic inflammatory responses are a critical pathological feature of fatal Ebola virus (EBOV) infection. While some inflammatory responses may originate from mononuclear phagocytes (MNPs), nonimmune cells vastly outnumber MNPs and may be an important source of inflammation. Here, we demonstrated that highly virulent EBOV induced a high and sustained pro-inflammatory response compared to less virulent ebolaviruses in non-MNPs through TLR4-independent NF-κB activation. We identified the EBOV matrix protein VP40 as a potent activator of NF-κB in non-MNPs, whose intrinsic inflammatory activation ability is higher than VP40 proteins from less virulent ebolaviruses. This suggests that VP40 is a virulence determinant inducing distinct degrees of pro-inflammatory responses among ebolaviruses. Mechanistically, VP40 activated the NF-κB signaling pathway, primarily via TNFR1 using a ligand-independent mechanism. These findings reveal mechanisms that may drive systemic inflammation and promote EBOV pathogenesis, suggesting potential therapeutic strategies to mitigate immune dysregulation in severe EBOV infections.
Virology—the path forward
Grönvall, Gigi Kwik , Lowen, Anice C. , Goodrum, Felicia , Alwine, James C. , Andersen, Kristian G. , Anthony, Simon J. , Baines, Joel D. , Banerjee, Arinjay , Broadbent, Andrew J. , Brooke, Christopher B. , Campos, Samuel K. , Caposio, Patrizia , Chan, Gary C. , Collins-McMillen, Donna , Connell, Nancy , Damania, Blossom , Daugherty, Matthew D. , Dermody, Terence S. , Galloway, Denise A. , Hartman, Amy L. , Hogue, Brenda G. , Jung, Jae U. , Karst, Stephanie M. , Laimins, Lou, Landais, Igor, Lindenbach, Brett D. , Luftig, Micah A. , Mehle, Andrew , Moscona, Anne , Münger, Karl , Nikolich‐Žugich, Janko , Popescu, Saskia , Racaniello, Vincent R. , Rice, Charles M. , Runstadler, Jonathan A. , Sapp, Martin , Scott, Rona S. , Streblow, Daniel N. , Doorslaer, Koenraad Van , White, Elizabeth , White, Timothy M. , Worobey, Michael , Yamaoka, Satoko , Rasmussen, Angela L , Gronvall, Gigi K , Lowen, Anice C , Goodrum, Felicia , Baines, Joel , Banerjee, Arinjay , Broadbent, Andrew J , Brooke, Christopher B , Campos, Samuel K , Caposio, Patrizia , Casadevall, Arturo , Chan, Gary C , Cliffe, Anna R , Damania, Blossom , Dermody, Terence S , DiMaio, Daniel , Duprex, W Paul , Greninger, Alexander L , Hartman, Amy L , Horner, Stacy M , Jung, Jae U , Kamil, Jeremy P , Laimins, Lou , Lakdawala, Seema S , Letko, Michael , Liu, Shan-Lu , Luftig, Micah , McFadden, Grant , Mehle, Andrew , Moscona, Anne , Munger, Joshua , Murphy, Eain , O'Connor, Christine M , Pekosz, Andrew , Permar, Sallie R , Pfeiffer, Julie K , Purdy, John G , Runstadler, Jonathan A , Sapp, Martin J , Scott, Rona S , Smith, Gregory A , Tibbetts, Scott A , Toth, Zsolt , Weiss, Susan R , White, Elizabeth A , Wobus, Christiane E , Yurochko, Andrew , Nikolich, Janko Z , Casadevall, Arturo , Debbink, Kari M. , Duprex, W. Paul , Emerman, Michael , Garry, Robert F. , Goldstein, Stephen A. , Greninger, Alexander L. , Hotez, Peter Jay , Morrison, Juliet , Mühlberger, Elke , Neufeldt, Christopher John , O’Connor, Christine M. , Permar, Sallie R. , Sorrell, Erin M. , Speranza, Emily E. , Wobus, Christiane E.
Journal of Virology | January 3, 2024 | Volume: 98 | Issue: 1 | Pages: No page available
ABSTRACT In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is a vital part of protecting the health, economy, and security of US citizens. Herein, we offer our perspectives on priorities for revised rules governing virology research in the US.