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Superresolution imaging of viral protein trafficking

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Abstract

The endoplasmic reticulum (ER) membrane is closely apposed to the outer mitochondrial membrane (OMM), which facilitates communication between these organelles. These contacts, known as mitochondria-associated membranes (MAM), facilitate calcium signaling, lipid transfer, as well as antiviral and stress responses. How cellular proteins traffic to the MAM, are distributed therein, and interact with ER and mitochondrial proteins are subject of great interest. The human cytomegalovirus UL37 exon 1 protein or viral mitochondria-localized inhibitor of apoptosis (vMIA) is crucial for viral growth. Upon synthesis at the ER, vMIA traffics to the MAM and OMM, where it reprograms the organization and function of these compartments. vMIA significantly changes the abundance of cellular proteins at the MAM and OMM, including proteins that regulate calcium homeostasis and cell death. Through the use of superresolution imaging, we have shown that vMIA is distributed at the OMM in nanometer scale clusters. This is similar to the clusters reported for the mitochondrial calcium channel, VDAC, as well as electron transport chain, translocase of the OMM complex, and mitochondrial inner membrane organizing system components. Thus, aside from addressing how vMIA targets the MAM and regulates survival of infected cells, biochemical studies and superresolution imaging of vMIA offer insights into the formation, organization, and functioning of MAM. Here, we discuss these insights into trafficking, function, and organization of vMIA at the MAM and OMM and discuss how the use of superresolution imaging is contributing to the study of the formation and trafficking of viruses.

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Acknowledgments

This work was partially funded by the NSF Grant (MCB 1244509) to ACP and JKJ. The confocal microscopy imaging was supported by a core Grant (1P30HD40677) to the Children’s Intellectual and Developmental Disabilities Research Center. This work was also supported by the Intramural Research Program of the National Institutes of Health including the National Institute of Biomedical Imaging and Bioengineering. We thank Kristen Rainey for assisting with imaging and analysis. We thank Andrew York and Hari Shroff for sharing MSIM analysis and deconvolution software. We thank Harald Hess for the use of the PALM analysis software, PeakSelector.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Center for Genetic Medicine Research, Children’s National Health System, 111 Michigan Ave, NW, Washington, DC, 20010, USA

    Anamaris M. Colberg-Poley, Kyle Salka, Shivaprasad Bhuvanendran & Jyoti K. Jaiswal

  2. Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA

    Anamaris M. Colberg-Poley & Jyoti K. Jaiswal

  3. Departments of Pediatrics and of Biochemistry and Molecular Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA

    Anamaris M. Colberg-Poley

  4. Section on Biophotonics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA

    George H. Patterson

  5. George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA

    David Yang

  6. Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA

    Jyoti K. Jaiswal

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  1. Anamaris M. Colberg-Poley
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Correspondence to Anamaris M. Colberg-Poley, George H. Patterson or Jyoti K. Jaiswal.

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This article is part of the Special Issue on Cytomegalovirus.

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Colberg-Poley, A.M., Patterson, G.H., Salka, K. et al. Superresolution imaging of viral protein trafficking. Med Microbiol Immunol 204, 449–460 (2015). https://doi.org/10.1007/s00430-015-0395-0

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