Mitochondria and Peroxisome Remodeling across Cytomegalovirus Infection Time Viewed through the Lens of Inter-ViSTA.

TitleMitochondria and Peroxisome Remodeling across Cytomegalovirus Infection Time Viewed through the Lens of Inter-ViSTA.
Publication TypeJournal Article
Year of Publication2020
AuthorsFederspiel, JD, Cook, KC, Kennedy, MA, Venkatesh, SS, Otter, CJ, Hofstadter, WA, Beltran, PMJean, Cristea, IM
JournalCell Rep
Volume32
Issue4
Pagination107943
Date Published2020 07 28
ISSN2211-1247
KeywordsCell Line, Computational Biology, Cytomegalovirus, Cytomegalovirus Infections, Endoplasmic Reticulum, Fibroblasts, Host Microbial Interactions, Humans, Immediate-Early Proteins, Mitochondria, Mitochondrial Membranes, Peroxisomes, Protein Interaction Maps
Abstract

<p>Nearly all biological processes rely on the finely tuned coordination of protein interactions across cellular space and time. Accordingly, generating protein interactomes has become routine in biological studies, yet interpreting these datasets remains computationally challenging. Here, we introduce Inter-ViSTA (Interaction Visualization in Space and Time Analysis), a web-based platform that quickly builds animated protein interaction networks and automatically synthesizes information on protein abundances, functions, complexes, and subcellular localizations. Using Inter-ViSTA with proteomics and molecular virology, we define virus-host interactions for the human cytomegalovirus (HCMV) anti-apoptotic protein, pUL37x1. We find that spatiotemporal controlled interactions underlie pUL37x1 functions, facilitating the pro-viral remodeling of mitochondria and peroxisomes during infection. Reciprocal isolations, microscopy, and genetic manipulations further characterize these associations, revealing the interplay between pUL37x1 and the MIB complex, which is critical for mitochondrial integrity. At the peroxisome, we show that pUL37x1 activates PEX11β to regulate fission, a key aspect of virus assembly and spread.</p>

DOI10.1016/j.celrep.2020.107943
Alternate JournalCell Rep
PubMed ID32726614
PubMed Central IDPMC8489195
Grant ListF31 AI147637 / AI / NIAID NIH HHS / United States
R01 GM114141 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States