Mitochondria and Peroxisome Remodeling across Cytomegalovirus Infection Time Viewed through the Lens of Inter-ViSTA. Author Joel Federspiel, Katelyn Cook, Michelle Kennedy, Samvida Venkatesh, Clayton Otter, William Hofstadter, Pierre Beltran, Ileana Cristea Publication Year 2020 Type Journal Article Abstract 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. Keywords Humans, Cell Line, Computational Biology, Cytomegalovirus, Cytomegalovirus Infections, Fibroblasts, Endoplasmic Reticulum, Mitochondria, Protein Interaction Maps, Immediate-Early Proteins, Peroxisomes, Host Microbial Interactions, Mitochondrial Membranes Journal Cell Rep Volume 32 Issue 4 Pages 107943 Date Published 2020 Jul 28 ISSN Number 2211-1247 DOI 10.1016/j.celrep.2020.107943 Alternate Journal Cell Rep PMCID PMC8489195 PMID 32726614 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML