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

Author(s): Hashimoto, Yutaka; Sheng, Xinlei; Murray-Nerger, Laura A; Cristea, Ileana M

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Abstract: 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.
Publication Date: 10-Feb-2020
Citation: Hashimoto, Y., Sheng, X., Murray-Nerger, L.A. et al. Temporal dynamics of protein complex formation and dissociation during human cytomegalovirus infection. Nat Commun 11, 806 (2020).
DOI: doi:10.1038/s41467-020-14586-5
ISSN: 2041-1723
EISSN: 2041-1723
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Nature Communications
Version: Final published version. This is an open access article.

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