@article{b0c11b1b97dd49dcaf9278039fd7e73a,
title = "The host exosome pathway underpins biogenesis of the human cytomegalovirus virion",
abstract = "Human Cytomegalovirus (HCMV) infects over half the world{\textquoteright}s population, is a leading cause of congenital birth defects, and poses serious risks for immuno-compromised individuals. To expand the molecular knowledge governing virion maturation, we analysed HCMV virions using proteomics, and identified a significant proportion of host exosome constituents. To validate this acquisition, we characterized exosomes released from uninfected cells, and demonstrated that over 99% of the protein cargo was subsequently incorporated into HCMV virions during infection. This suggested a common membrane origin, and utilization of host exosome machinery for virion assembly and egress. Thus, we selected a panel of exosome proteins for knock down, and confirmed that loss of 7/9 caused significantly less HCMV production. Saliently, we report that VAMP3 is essential for viral trafficking and release of infectious progeny, in various HCMV strains and cell types. Therefore, we establish that the host exosome pathway is intrinsic for HCMV maturation, and reveal new host regulators involved in viral trafficking, virion envelopment, and release. Our findings underpin future investigation of host exosome proteins as important modulators of HCMV replication with antiviral potential.",
author = "Turner, {Declan L.} and Korneev, {Denis V.} and Purdy, {John G.} and {de Marco}, Alex and Mathias, {Rommel A.}",
note = "Funding Information: We thank the Monash Micro Imaging Platform, the Ramaciotti Centre for Cryo-Electron Microscopy, and the Monash Biomedical Proteomics Facility. We also thank Prof. Ileana Cristea for providing access to mass spectrometry instrumentation (DP1DA026192). We would like to thank Prof. Stephen Turner, Dr. Nathan Croft, and Dr. Chris Andoniou for critical reading of the manuscript. DLT was supported by an Australian Government Research Training Program (RTP) Stipend and RTP Fee-Off-set Scholarship through Monash University. This work was supported by the National Health and Medical Research Council of Australia (# APP1100737 to RAM). Funding Information: We thank the Monash Micro Imaging Platform, the Ramaciotti Centre for Cryo-Electron Microscopy, and the Monash Biomedical Proteomics Facility. We also thank Prof. Ileana Cristea for providing access to mass spectrometry instrumentation (DP1DA026192). We would like to thank Prof. Stephen Turner, Dr. Nathan Croft, and Dr. Chris Andoniou for critical reading of the manuscript. DLT was supported by an Australian Government Research Training Program (RTP) Stipend and RTP Fee-Offset Scholarship through Monash University. This work was supported by the National Health and Medical Research Council of Australia (# APP1100737 to RAM). Publisher Copyright: {\textcopyright} Turner et al.",
year = "2020",
month = sep,
doi = "10.7554/ELIFE.58288",
language = "English (US)",
volume = "9",
pages = "1--29",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}