Herpes simplex virus nucleocapsids mature to progeny virions by an envelopment -> deenvelopment -> reenvelopment pathway

Herpes simplex virus (HSV) nucleocapsids acquire an envelope by budding thr ough the inner nuclear membrane, but it is uncertain whether this envelope is retained during virus maturation and egress or whether mature progeny vi rions are derived by deenvelopment at the outer nuclear membrane followed b y reenvelopment in a cytoplasmic compartment, To resolve this issue, we use d immunogold electron microscopy to examine the distribution of glycoprotei n D (gD) in cells infected with HSV-1 encoding a wild-type go or a go which is retrieved to the endoplasmic reticulum (ER). In cells infected with wil d-type HSV-1, extracellular virions and virions in the perinuclear space bo und approximately equal amounts of go antibody. In cells infected with HSV- I encoding an ER-retrieved go, the inner and outer nuclear membranes were h eavily gold labeled, as were perinuclear enveloped virions. Extracellular v irions exhibited very little gold decoration (10- to 30-fold less than peri nuclear virions). We conclude that the envelope of perinuclear virions must be lost during maturation and egress and that mature progeny virions must acquire an envelope from a post-ER cytoplasmic compartment, We noted also t hat go appears to be excluded from the plasma membrane in cells infected wi th wild-type virus.