Egress of human cytomegalovirus through multivesicular bodies

Human Cytomegalovirus (HCMV) can infect a variety of cell types by using virions of varying glycoprotein composition. It is unclear how this diversity is generated, but spatiotemporally separated envelopment and egress pathways might play a role. So far, one egress pathway has been described in which HCMV particles are separately enveloped into individual vesicles and continuously exocytosed. However, some studies have also found enveloped virus particles inside multivesicular bodies (MVBs) but could not link them to productive egress or degradation pathways. We used a novel 3D-CLEM workflow to investigate MVBs in HCMV morphogenesis and egress. We found that HCMV envelopment occurred at MVBs and that virus-filled MVBs traversed the cytoplasm to release virions in bulk at the plasma membrane to form extracellular virus accumulations. Our data support the existence of a novel bona fide HCMV egress pathway, which opens the gate to evaluate divergent egress pathways in generating virion diversity. ### Competing Interest Statement The authors have declared no competing interest.