Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease.

ABSTRACT: Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1^-/- mice results in replication of HSV-1 and Asah1^-/- mice die soon after

SUBMITTER: Lang J 

PROVIDER: S-EPMC7067866 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature