tetano
Editor, Senior Moderator
PLoS One
. 2026 Apr 29;21(4):e0348065.
doi: 10.1371/journal.pone.0348065. eCollection 2026.
Poldip2 deficiency attenuates lung disease severity in a mouse model of COVID-19
Ruinan Hu[SUP] 1 [/SUP], Alejandra Valdivia[SUP] 1 [/SUP], Taylor White[SUP] 1 [/SUP], Willy Ju[SUP] 2 [/SUP], Maegan L Brockman[SUP] 1 [/SUP], Zhan Zhang[SUP] 1 [/SUP], Hongyan Qu[SUP] 1 [/SUP], Georgette Gafford[SUP] 1 [/SUP], Giji Joseph[SUP] 1 [/SUP], Samantha Burton[SUP] 3 [/SUP], Leda Bassit[SUP] 4 [/SUP], Tysheena P Charles[SUP] 3 [/SUP], Raymond F Schinazi[SUP] 4 [/SUP], Rebecca D Levit[SUP] 1 [/SUP], Cynthia A Derdeyn[SUP] 5 [/SUP], Kathy K Griendling[SUP] 1 [/SUP], Bernard Lassègue[SUP] 1 [/SUP], Marina S Hernandes[SUP] 1 [/SUP]
Affiliations
The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the infection resulting in lung inflammation, pulmonary vascular leakage and diffuse alveolar damage. Polymerase delta-interacting protein-2 (Poldip2) mediates lung inflammation and vascular permeability after lipopolysaccharide-induced acute respiratory distress syndrome; however, whether it also affects the pathological consequences of SARS-CoV-2 infection is completely unknown. Here, we assessed the role of Poldip2 in inflammation, immune cell infiltration and lung tissue damage in response to SARS-CoV-2. Our data show that Poldip2 expression was elevated in human lung vascular endothelium after infection. In a Poldip2-deficient heterozygous mouse model, acute clinical symptoms were not affected. However, seven days after infection, Poldip2 knockdown reduced viral load, decreased infiltration of myeloperoxidase (MPO)-positive neutrophils into inflamed lungs, and reduced tissue damage. Poldip2 also modulated the inflammatory response to viral infection in a heterogeneous manner, reflecting its diverse regulatory roles. These data support the concept that targeting Poldip2 could potentially attenuate severe lung injury following SARS-CoV-2 infection.
. 2026 Apr 29;21(4):e0348065.
doi: 10.1371/journal.pone.0348065. eCollection 2026.
Poldip2 deficiency attenuates lung disease severity in a mouse model of COVID-19
Ruinan Hu[SUP] 1 [/SUP], Alejandra Valdivia[SUP] 1 [/SUP], Taylor White[SUP] 1 [/SUP], Willy Ju[SUP] 2 [/SUP], Maegan L Brockman[SUP] 1 [/SUP], Zhan Zhang[SUP] 1 [/SUP], Hongyan Qu[SUP] 1 [/SUP], Georgette Gafford[SUP] 1 [/SUP], Giji Joseph[SUP] 1 [/SUP], Samantha Burton[SUP] 3 [/SUP], Leda Bassit[SUP] 4 [/SUP], Tysheena P Charles[SUP] 3 [/SUP], Raymond F Schinazi[SUP] 4 [/SUP], Rebecca D Levit[SUP] 1 [/SUP], Cynthia A Derdeyn[SUP] 5 [/SUP], Kathy K Griendling[SUP] 1 [/SUP], Bernard Lassègue[SUP] 1 [/SUP], Marina S Hernandes[SUP] 1 [/SUP]
Affiliations
- PMID: 42054341
- DOI: 10.1371/journal.pone.0348065
The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the infection resulting in lung inflammation, pulmonary vascular leakage and diffuse alveolar damage. Polymerase delta-interacting protein-2 (Poldip2) mediates lung inflammation and vascular permeability after lipopolysaccharide-induced acute respiratory distress syndrome; however, whether it also affects the pathological consequences of SARS-CoV-2 infection is completely unknown. Here, we assessed the role of Poldip2 in inflammation, immune cell infiltration and lung tissue damage in response to SARS-CoV-2. Our data show that Poldip2 expression was elevated in human lung vascular endothelium after infection. In a Poldip2-deficient heterozygous mouse model, acute clinical symptoms were not affected. However, seven days after infection, Poldip2 knockdown reduced viral load, decreased infiltration of myeloperoxidase (MPO)-positive neutrophils into inflamed lungs, and reduced tissue damage. Poldip2 also modulated the inflammatory response to viral infection in a heterogeneous manner, reflecting its diverse regulatory roles. These data support the concept that targeting Poldip2 could potentially attenuate severe lung injury following SARS-CoV-2 infection.