Patterns of Autologous and Nonautologous Interactions between Core Nuclear Egress Complex (NEC) Proteins of α-, β- and γ-Herpesviruses

Viruses

SusanneM. Bailer¹  Eric Sonntag²  Jens Milbradt²  Sigrun Häge²  Pierre Tannig²  Regina Müller²  Christina Wangen²  Manfred Marschall²  Lisa Seyler³  Tobias Bäuerle³  EvaMaria Borst⁴  Chung-Pei Lee⁵ 

[1] Fraunhofer Institute for Interfacial Engineering and Biotechnology and Institute for Interfacial Engineering and Plasma Technology IGVP, University of Stuttgart, 70569 Stuttgart, Germany;Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany;Institute of Radiology, University Medical Center Erlangen, 91054 Erlangen, Germany;Institute of Virology, Hannover Medical School, 30625 Hannover, Germany;School of Nursing, National Taipei University of Nursing and Health Sciences, 11219 Taipei, Taiwan;

关键词: α-, β- and γ-herpesviruses;    core nuclear egress complexes (necs);    degree of conservation;    core nec interaction properties;    autologous vs. nonautologous interactions;    multicomponent nec recruitment of proteins;    takeover of activities in vitro and in vivo;    functional complementarity;   

DOI  :  10.3390/v12030303

来源: DOAJ

【 摘 要 】

Nuclear egress is a regulated process shared by α-, β- and γ-herpesviruses. The core nuclear egress complex (NEC) is composed of the membrane-anchored protein homologs of human cytomegalovirus (HCMV) pUL50, murine cytomegalovirus (MCMV) pM50, Epstein−Barr virus (EBV) BFRF1 or varicella zoster virus (VZV) Orf24, which interact with the autologous NEC partners pUL53, pM53, BFLF2 or Orf27, respectively. Their recruitment of additional proteins leads to the assembly of a multicomponent NEC, coordinately regulating viral nucleocytoplasmic capsid egress. Here, the functionality of VZV, HCMV, MCMV and EBV core NECs was investigated by coimmunoprecipitation and confocal imaging analyses. Furthermore, a recombinant MCMV, harboring a replacement of ORF M50 by UL50, was analyzed both in vitro and in vivo. In essence, core NEC interactions were strictly limited to autologous NEC pairs and only included one measurable nonautologous interaction between the homologs of HCMV and MCMV. A comparative analysis of MCMV-WT versus MCMV-UL50-infected murine fibroblasts revealed almost identical phenotypes on the levels of protein and genomic replication kinetics. In infected BALB/c mice, virus spread to lung and other organs was found comparable between these viruses, thus stating functional complementarity. In conclusion, our study underlines that herpesviral core NEC proteins are functionally conserved regarding complementarity of core NEC interactions, which were found either virus-specific or restricted within subfamilies.

【 授权许可】

Unknown