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Article
Protein-protein interactions suggest novel activities of human cytomegalovirus tegument protein pUL103
Journal of Virology (2016)
  • Daniel A. Ortiz, Wayne State University
  • James E. Glassbrook, Wayne State University
  • Philip E. Pellett, Wayne State University
Abstract
uman cytomegalovirus (HCMV) is an enveloped double-stranded DNA virus that causes severe disease in newborns and immunocompromised patients. During infection, the host cell endosecretory system is remodeled to form the cytoplasmic virion assembly complex (cVAC). We and others previously identified the conserved, multifunctional HCMV virion tegument protein pUL103 as important for cVAC biogenesis and efficient secondary envelopment. To help define its mechanisms of action and predict additional functions, we used two complementary methods, coimmunoprecipitation (co-IP) and proximity biotinylation (BioID), to identify viral and cellular proteins that interact with pUL103. By using the two methods in parallel and applying stringent selection criteria, we identified potentially high-value interactions of pUL103 with 13 HCMV and 18 cellular proteins. Detection of the previously identified pUL103-pUL71 interaction, as well as verification of several interactions by reverse co-IP, supports the specificity of our screening process. As might be expected for a tegument protein, interactions were identified that suggest distinct roles for pUL103 across the arc of lytic infection, including interactions with proteins involved in cellular antiviral responses, nuclear activities, and biogenesis and transport of cytoplasmic vesicles. Further analysis of some of these interactions expands our understanding of the multifunctional repertoire of pUL103: we detected HCMV pUL103 in nuclei of infected cells and identified an ALIX-binding domain within the pUL103 sequence.
Publication Date
September 1, 2016
DOI
10.1128/JVI.00097-16
Citation Information
Ortiz DA, Glassbrook JE, Pellett PE. Protein-Protein Interactions Suggest Novel Activities of Human Cytomegalovirus Tegument Protein pUL103. J Virol. 2016 Aug 12;90(17):7798-810. doi: 10.1128/JVI.00097-16. PMID: 27334581; PMCID: PMC4988140.