The host exosome biogenesis pathway is essential for human cytomegalovirus virion assembly and egress

ABSTRACT: Human Cytomegalovirus (HCMV) infects over 50% of humans, is a leading cause of congenital birth defects, and poses serious risks for immuno-compromised individuals. To expand the molecular knowledge governing virion assembly and egress, we initiated a proteomics-based investigation and identified a significant proportion of host exosome constituents in HCMV virions. Quantitative analysis of exosomes released from uninfected cells (765 proteins) revealed that over 99% of the protein cargo was subsequently integrated into virions, confirming near-complete acquisition of exosome biogenesis during infection. We confirmed VAMP3 is essential for viral trafficking and release of infectious progeny, further validating the intrinsic exploitation of the pathway by HCMV. Therefore, host exosomes serve as the molecular template for virion cargo addition, and provide an export mechanism for virion egress. Our discovery underpins future investigation of host exosome proteins as important modulators of viral maturation, and enhances the understanding of HCMV envelopment, trafficking, fusion and release.

INSTRUMENT(S): Orbitrap Fusion ETD, LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human) Human Cytomegalovirus (strain Ad169) (hhv-5) (human Herpesvirus 5)

SUBMITTER: Rommel Mathias  

LAB HEAD: Rommel Mathias

PROVIDER: PXD015081 | Pride | 2021-02-22

REPOSITORIES: Pride