Fig. 1: HCMV globally modulates organelle contact protein abundances in contrast to infections with HSV-1, Infl. A, and HCoV-OC43.
From: Restructured membrane contacts rewire organelles for human cytomegalovirus infection
A Schematic highlighting the organelle remodeling events that underlie the unique infectious cycles of HCMV, HSV-1, Infl. A, and HCoV-OC43, which vary in structure (left), size, and replication timescale (right). B Membrane contact sites, facilitated by protein interactions, enable the direct transfer of biomolecules to coordinately regulate organelle structure and function. MCS-PRM simultaneously quantifies the abundances of MCS protein tethers, regulators, and functional interactors across organelles, identifying alterations to the extent and functions of organelle contacts. C MCS-PRM quantification of MCS protein abundances during infections (MOI: multiplicity of infection, i.e., number of viral particles per cell) with HCMV (MOI = 3, N = 6), HSV-1 (MOI = 10, N = 4), Infl. A (MOI = 0.8, N = 3), and HCoV-OC43 (MOI = 5, N = 3). Timepoints are indicated at left, proteins measured are top, grouped by primary function, and heatmap key is above (Log2 scale). The rationale for proteins included in MCS-PRM can be found in Supplementary Table 1. D. Average peptide abundances (scaled to mean = 1) of MCS proteins grouped by localization (color/order key at top) and plotted across infection time (x-axis, grey triangles). Black points are proteins, bold lines connect the median of each timepoint, dotted grey lines represent median abundance in the uninfected state, and numbers indicate the maximum fold-change observed for the given MCS (****p ≤ 0.0001, ***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05, N.S. is p > 0.05 by two-way ANOVA across all timepoints and a Dunnett’s multiple comparisons test to Mock). Specific p-values are as follows, from left to right (ER-Mito to Perox-LD) for each infection: HCMV p ≤ 0.0001, p = 0.0004, p ≤ 0.0001, p ≤ 0.0001, p = 0.0024, p = 0.0002, p = 0.0026, p = 0.0018; HSV-1 p = 0.0269, p = 0.0373, N.S., p = 0.0086, N.S., p = 0.0025, N.S., N.S.; Influenza A p ≤ 0.0001, p = 0.0008, p = 0.0274, p = 0.0001, N.S., p = 0.0052, N.S., N.S.; HCoV-OC43 p ≤ 0.0001, p ≤ 0.0001, p = 0.0004, p ≤ 0.0001, p = 0.0003, p = 0.0002, p = 0.0046, N.S.
