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Article Dans Une Revue Molecular and Cellular Proteomics Année : 2014

Proteomic analysis of the multimeric nuclear egress complex of human cytomegalovirus

Résumé

Herpesviral capsids are assembled in the host cell nucleusbefore being translocated into the cytoplasm for further maturation. The crossing of the nuclear envelope represents a major event that requires the formation of the nuclear egress complex (NEC). Previous studies demonstrated that human cytomegalovirus (HCMV) proteins pUL50 and pUL53, as well as their homologs in all members of Herpesviridae, interact with each other at the nuclear envelope and form the heterodimeric core of the NEC. In order to characterize further the viral and cellular protein content of the multimeric NEC, the native complex was isolated from HCMV-infected human primary fibroblasts at various time points and analyzed using quantitative proteomics. Previously postulated components of the HCMVspecific NEC, as well as novel potential NEC-associated proteins such as emerin, were identified. In this regard, interaction and colocalization between emerin and pUL50 were confirmed by coimmunoprecipitation and confocal microscopy analyses, respectively. A functional validation of viral and cellular NEC constituents was achieved through siRNA-mediated knockdown experiments. The important role of emerin in NEC functionality was demonstrated by a reduction of viral replication when emerin expression was down-regulated. Moreover, under such conditions, reduced production of viral proteins and deregulation of viral late cytoplasmic maturation were observed. Combined, these data prove the functional importance of emerin as an NEC component, associated with pUL50, pUL53, pUL97, p32/ gC1qR, and further regulatory proteins. Summarized, our findings provide the first proteomics-based characterization and functional validation of the HCMV-specific multimeric NEC. Molecular & Cellular Proteomics 13: 10.1074/ mcp.M113.035782, 2132–2146, 2014.
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hal-02083913 , version 1 (01-03-2023)

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Jens Milbradt, Alexandra Kraut, Corina Hutterer, Eric Sonntag, Cathrin Schmeiser, et al.. Proteomic analysis of the multimeric nuclear egress complex of human cytomegalovirus. Molecular and Cellular Proteomics, 2014, 13 (8), pp.2132-2146. ⟨10.1074/mcp.M113.035782⟩. ⟨hal-02083913⟩
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