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The human cytomegalovirus nuclear egress complex unites multiple functions: Recruitment of effectors, nuclear envelope rearrangement, and docking to nuclear capsids
Author(s) -
Marschall Manfred,
Muller Yves A.,
Diewald Benedikt,
Sticht Heinrich,
Milbradt Jens
Publication year - 2017
Publication title -
reviews in medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.06
H-Index - 90
eISSN - 1099-1654
pISSN - 1052-9276
DOI - 10.1002/rmv.1934
Subject(s) - biology , nuclear lamina , capsid , herpes simplex virus , computational biology , effector , nuclear transport , virology , viral replication , virus , microbiology and biotechnology , nuclear protein , genetics , cell nucleus , cytoplasm , gene , transcription factor
Summary Background Nuclear replication represents a common hallmark of herpesviruses achieved by a number of sequentially unrolled regulatory processes. A rate‐limiting step is provided by nucleo‐cytoplasmic capsid export, for which a defined multiregulatory protein complex, namely, the nuclear egress complex (NEC), is assembled comprising both viral and cellular components. The NEC regulates at least 3 aspects of herpesviral nuclear replication: (1) multimeric recruitment of NEC‐associated effector proteins, (2) reorganization of the nuclear lamina and membranes, and (3) the docking to nuclear capsids. Here, we review published data and own experimental work that characterizes the NEC of HCMV and other herpesviruses. Methods A systematic review of information on nuclear egress of HCMV compared to selected alpha‐, beta‐, and gamma‐herpesviruses: proteomics‐based approaches, high‐resolution imaging techniques, and functional investigations. Results A large number of reports on herpesviral NECs have been published during the last two decades, focusing on protein‐protein interactions, nuclear localization, regulatory phosphorylation, and functional validation. The emerging picture provides an illustrated example of well‐balanced and sophisticated protein networking in virus‐host interaction. Conclusions Current evidence refined the view about herpesviral NECs. Datasets published for HCMV, murine CMV, herpes simplex virus, and Epstein‐Barr virus illustrate the marked functional consistency in the way herpesviruses achieve nuclear egress. However, this compares with only limited sequence conservation of core NEC proteins and a structural conservation restricted to individual domains. The translational use of this information might help to define a novel antiviral strategy on the basis of NEC‐directed small molecules.