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Human Cytomegalovirus Utilizes Extracellular Vesicles To Enhance Virus Spread.

Nicholas T Streck1, Yuanjun Zhao2, Jeffrey M Sundstrom2

  • 1Department of Microbiology & Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.

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|June 12, 2020
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Summary

Human cytomegalovirus (HCMV) manipulates extracellular vesicles (EVs) by upregulating ESCRT proteins, increasing their release and enhancing virus spread to new cells. This study reveals a novel mechanism of HCMV-induced host cell alteration.

Keywords:
CD63ESCRTsGW4869HCMVextracellular vesiclesspread

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Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Human cytomegalovirus (HCMV) infection impacts cellular secretory pathways for replication.
  • The role of extracellular vesicles (EVs) in HCMV spread is not well understood.
  • Viruses often alter EVs, influencing infection dynamics.

Purpose of the Study:

  • To investigate how HCMV infection alters the cellular environment to promote virus spread.
  • To determine the role of extracellular vesicles (EVs) in HCMV transmission.

Main Methods:

  • Upregulation of endosomal sorting complex required for transport (ESCRT) proteins in HCMV-infected cells.
  • Analysis of EV biogenesis and release from infected fibroblasts.
  • Treatment with EV inhibitor GW4869 to assess impact on HCMV spread.
  • Transfer of EVs purified from infected cells to evaluate their effect on virus spread.

Main Results:

  • HCMV infection upregulates ESCRT proteins, increasing EV biogenesis and release.
  • HCMV-infected fibroblasts exhibit altered EV size and increased vesicle release.
  • Inhibition of EV production via GW4869 reduced HCMV spread efficiency.
  • EVs from HCMV-infected cells enhanced virus spread to uninfected cells.

Conclusions:

  • HCMV manipulates EV pathways, specifically upregulating ESCRT, to enhance virus spread.
  • Altered EVs transfer proviral signals, priming recipient cells for infection.
  • This represents a novel host manipulation strategy by HCMV to increase transmission efficiency.