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

Federspiel, Joel D; Cook, Katelyn C; Kennedy, Michelle A; Venkatesh, Samvida S; Otter, Clayton J; Hofstadter, William A; Jean Beltran, Pierre M; Cristea, Ileana M

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.