Herpes simplex viruses activate phospholipid scramblase to redistribute phosphatidylserines and Akt to the outer leaflet of the plasma membrane and promote viral entry

PLoS Pathogens

Carl Pierce¹  Natalia Cheshenko²  Betsy C. Herold³ 

[1]Department of Microbiology-Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America

[2]Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, United States of America

[3]Louisiana State University Health Sciences Center, UNITED STATES

DOI  :  10.1371/journal.ppat.1006766

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Herpes simplex virus (HSV) entry is associated with Akt translocation to the outer leaflet of the plasma membrane to promote a complex signaling cascade. We hypothesized that phospholipid scramblase-1 (PLSCR1), a calcium responsive enzyme that flips phosphatidylserines between membrane leaflets, might redistribute Akt to the outside during entry. Confocal imaging, biotinylation of membrane proteins and flow cytometric analysis demonstrated that HSV activates PLSCR1 and flips phosphatidylserines and Akt to the outside shortly following HSV-1 or HSV-2 exposure. Translocation was blocked by addition of a cell permeable calcium chelator, pharmacological scramblase antagonist, or transfection with small interfering RNA targeting PLSCR1. Co-immunoprecipitation and proximity ligation studies demonstrated that PLSCR1 associated with glycoprotein L at the outer leaflet and studies with gL deletion viruses indicate that this interaction facilitates subsequent restoration of the plasma membrane architecture. Ionomycin, a calcium ionophore, also induced PLSCR1 activation resulting in Akt externalization, suggesting a previously unrecognized biological phenomenon.

【 授权许可】

CC BY