Related Experiment Video

Updated: Sep 1, 2025

Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
05:53

Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates

Published on: July 6, 2013

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Restructured membrane contacts rewire organelles for human cytomegalovirus infection

Katelyn C Cook1, Elene Tsopurashvili1, Jason M Needham2

  • 1Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, US.

Nature Communications
|August 11, 2022
PubMed

Insights

Viruses alter organelle connections called membrane contact sites (MCSs) to control cell functions. This study reveals how human cytomegalovirus (HCMV) manipulates MCSs, like the mitochondria-ER encapsulation structure (MENC), to promote its replication.

Area of Science:

  • Cell Biology
  • Virology
  • Proteomics

Background:

  • Membrane contact sites (MCSs) are crucial for organelle communication and cellular functions.
  • Viral infections extensively remodel host organelles, but their impact on MCSs is poorly understood.
  • Human cytomegalovirus (HCMV) is an ancient beta-herpesvirus known to manipulate cellular processes.

Purpose of the Study:

  • To develop a platform for simultaneously measuring MCS proteins across all organelles.
  • To investigate virus-driven alterations of MCSs during HCMV infection.
  • To understand the role of specific MCS structures, like MENCs, in viral replication.

Main Methods:

  • Developed a targeted proteomics platform to quantify MCS proteins at all organelles.
  • Employed super-resolution microscopy for visualizing MCS structures.
  • Compared findings across infections with HCMV, HSV-1, Influenza A, and HCoV-OC43.

Main Results:

  • Discovered a stabilized mitochondria-ER encapsulation structure (MENC) that becomes predominant during HCMV infection.
  • Showed that MENCs recruit VAP-B and PTPIP51 to support viral production.
  • Revealed that premature ER-mitochondria tethering triggers STING and interferon responses, hindering viral infection; ACBD5 impacts peroxisome dynamics and viral titers.

Conclusions:

  • HCMV dynamically regulates MCSs, switching organelle functions from anti-viral to pro-viral.
  • The MENC structure is a key viral manipulation enabling HCMV replication.
  • Targeting MCSs, like ACBD5-mediated contacts, offers potential antiviral strategies.

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