Abstract
Herpesviruses assemble capsids in the nucleus and egress by unconventional vesicle-mediated trafficking through the nuclear envelope. Capsids bud at the inner nuclear membrane into the nuclear envelope lumen. The resulting intralumenal vesicles fuse with the outer nuclear membrane, delivering the capsids to the cytoplasm. Two viral proteins are required for vesicle formation, the tail-anchored pUL34 and its soluble interactor, pUL31. Whether cellular proteins are involved is unclear. Using giant unilamellar vesicles, we show that pUL31 and pUL34 are sufficient for membrane budding and scission. pUL34 function can be bypassed by membrane tethering of pUL31, demonstrating that pUL34 is required for pUL31 membrane recruitment but not for membrane remodeling. pUL31 can inwardly deform membranes by oligomerizing on their inner surface to form buds that constrict to vesicles. Therefore, a single viral protein can mediate all events necessary for membrane budding and abscission.
Highlights
Herpesviruses egress from the nucleus by vesicle trafficking through the nuclear envelope
We show that pUL31 and pUL34 are sufficient for membrane budding and scission. pUL34 function can be bypassed by membrane tethering of pUL31, demonstrating that pUL34 is required for pUL31 membrane recruitment but not for membrane remodeling. pUL31 can inwardly deform membranes by oligomerizing on their inner surface to form buds that constrict to vesicles
We show that the two viral proteins are sufficient for budding and fission of membrane vesicles into the lumen of giant unilamellar vesicles (GUVs), a process that is topologically identical to inwardly directed vesicle formation at the inner nuclear membrane during herpesvirus nuclear egress
Summary
Herpesviruses egress from the nucleus by vesicle trafficking through the nuclear envelope. PUL31-pUL34-mediated inner nuclear membrane engulfment, much like the suggested pathway for nuclear egress of large ribonucleoprotein complexes identified recently in Drosophila [24], represents one of these exceptional pathways It involves vesicle budding and scission from the nucleoplasm into the intermembrane space of the nuclear envelope, which is connected and topologically identical to the lumen of the endoplasmic reticulum. The molecular machinery mediating inner nuclear membrane deformation and scission remains largely obscure It is especially unclear whether it requires proteins within the lumen of the nuclear envelope that could assemble a coat on the outer surface of the nascent vesicles, similar to COP I, COP II, and clathrin coats in the cytoplasm. We reconstituted the function of pseudorabies virus pUL31 and pUL34 in a simple membrane system by using giant unilamellar vesicles (GUVs) mimicking the lipid composition of the
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