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

TitleTemporal dynamics of protein complex formation and dissociation during human cytomegalovirus infection.
Publication TypeJournal Article
Year of Publication2020
AuthorsHashimoto, Y, Sheng, X, Murray-Nerger, LA, Cristea, IM
JournalNat Commun
Date Published2020 Feb 10
KeywordsCell Line, Cytomegalovirus, Cytomegalovirus Infections, Fatty Acids, Host-Pathogen Interactions, Humans, Immunologic Factors, Integrin beta1, Phosphatidylinositol 3-Kinases, Protein Aggregation, Pathological, Protein Biosynthesis, Protein Interaction Maps, Protein Stability, Proteomics, Receptor, IGF Type 2, Signal Transduction, Tetraspanin 30, Viral Proteins, Virus Replication

<p>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 dissociation of hundreds of functional protein complexes and the dynamics of host-host, virus-host, and virus-virus PPIs. We establish pro-viral roles for cellular protein complexes and translocating proteins. We show the HCMV receptor integrin beta 1 dissociates from extracellular matrix proteins, becoming internalized with CD63, which is necessary for virus production. Moreover, this approach facilitates characterization of essential viral proteins, such as pUL52. This study of temporal protein complex dynamics provides insights into mechanisms of HCMV infection and a resource for biological and therapeutic studies.</p>

Alternate JournalNat Commun
PubMed ID32041945
PubMed Central IDPMC7010728
Grant ListR01 GM114141 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States