Abstract
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.
Footnotes
↵* Jens B. Bosse, Center for Structural Systems Biology, Notkestraße 85, 22607 Hamburg Email: jens.bernhard.bosse{at}cssb-hamburg.de
For this version of the manuscript we added additional experiments in figure 1 to show the prevalence of the phenotype investigated in this study. Further, to make the assesment of our EM data easier, we added the supplementary figures 1, 2 and 3. All figures have been updated and rearranged to best suit a digital format. A model has been added in figure 6 for clarity. All text sections have been updated to clarify the findings of the study and the biological implications.