Dataset Information

Temporal dynamics of protein complex formation and dissociation during human cytomegalovirus infection

ABSTRACT: Emerging evidence indicates that viral infection alters protein complex composition to induce both proviral and antiviral effects. However, global changes in protein complexes during infection remains understudied. Here, we employ thermal proximity coaggregation (TPCA) analysis to provide the first global and temporal characterization of changes in protein complexes during human cytomegalovirus (HCMV) infection. This dataset provides a resource to mine the alterations in protein complexes during HCMV infection. Furthermore, our subsequent experiments identified that these changes in protein complex composition and interactions functionally contribute to the progression of infection.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human) Human Cytomegalovirus (strain Ad169) (hhv-5) (human Herpesvirus 5)

TISSUE(S): Cell Culture, Fibroblast

SUBMITTER: Yutaka Hashimoto

LAB HEAD: Ileana M. Cristea

PROVIDER: PXD014747 | Pride | 2020-01-29

REPOSITORIES: Pride

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Publications

Temporal dynamics of protein complex formation and dissociation during human cytomegalovirus infection.

Hashimoto Yutaka Y Sheng Xinlei X Murray-Nerger Laura A LA Cristea Ileana M IM

Nature communications 20200210 1

The co-evolution and co-existence of viral pathogens with their hosts for millions of years is reflected in dynamic virus-host protein-protein interactions (PPIs) that are intrinsic to the spread of infections. Here, we investigate the system-wide dynamics of protein complexes throughout infection with the herpesvirus, human cytomegalovirus (HCMV). Integrating thermal shift assays and mass spectrometry quantification with virology and microscopy, we monitor the temporal formation and dissociatio ...[more]

PMID: 32041945

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Project description:Human CMV (hCMV) establishes lifelong infections in most of us, causing developmental defects in human embryos and life-threatening disease in immunocompromised individuals. During productive infection, the viral >230,000-bp dsDNA genome is expressed widely and in a temporal cascade. The hCMV genome does not carry histones when encapsidated but has been proposed to form nucleosomes after release into the host cell nucleus. Here, we present hCMV genome-wide nucleosome occupancy and nascent transcript maps during infection of permissive human primary cells. We show that nucleosomes occupy nuclear viral DNA in a nonrandom and highly predictable fashion. At early times of infection, nucleosomes associate with the hCMV genome largely according to their intrinsic DNA sequence preferences, indicating that initial nucleosome formation is genetically encoded in the virus. However, as infection proceeds to the late phase, nucleosomes redistribute extensively to establish patterns mostly determined by nongenetic factors. We propose that these factors include key regulators of viral gene expression encoded at the hCMV major immediate-early (IE) locus. Indeed, mutant virus genomes defcient for IE1 expression exhibit globally increased nucleosome loads and reduced nucleosome dynamics compared with WT genomes. The temporal nucleosome occupancy differences between IE1-defcient and WT viruses correlate inversely with changes in the pattern of viral nascent and total transcript accumulation. These results provide a framework of spatial and temporal nucleosome organization across the genome of a major human pathogen and suggest that an hCMV major IE protein governs overall viral chromatin structure and function. [i] H3 ChIP-chip measurements of WT human cytomegalovirus (strain TB40E) following infection of MRC-5 cells. WT 8 hours postinfection, with corresponding mock IgG input control: 3 replicates; WT virus, 48 hours postinfection with corresponding mock IgG input contro: 3 replicates. [ii] MNase-chip measurements of WT and dlIE1 human cytomegalovirus nucleosomes following infection of MRC-5 cells. WT 8 hours postinfection, with corresponding sonicated DNA input control: 6 replicates; WT virus 48 hours postinfection, with corresponding sonicated DNA input control: 6 replicates; WT 96 hours postinfection, with corresponding sonicated DNA input control: 2 replicates; dlIE1 virus 8 hours postinfection, with corresponding sonicated DNA input control: 2 replicates; dlIE1 virus 96 hours postinfection, with corresponding sonicated DNA input control: 2 replicates. [iii] Total and nascent RNA measurements of WT and dlIE1 human cytomegalovirus transcripts following infection of MRC-5 cells. WT 8 hours postinfection: 2 replicates; WT virus 96 hours postinfection: 2 replicates; dlIE1 8 hours postinfection: 2 replicates; dlIE1 virus 96 hours postinfection: 2 replicates; sonicated DNA input control: 10 replicates.

Dataset Information

Temporal dynamics of protein complex formation and dissociation during human cytomegalovirus infection

Publications

Temporal dynamics of protein complex formation and dissociation during human cytomegalovirus infection.

Similar Datasets

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