title: Remodelling of the nuclear lamina during human cytomegalovirus infection: role of the viral proteins pUL50 and pUL53.
abstract: A fundamental step in the efficient production of human cytomegalovirus (HCMV) progeny is viral egress from the nucleus to the cytoplasm of infected cells. In the family Herpesviridae, this process involves alteration of nuclear lamina components by two highly conserved proteins, whose homologues in HCMV are named pUL50 and pUL53. This study showed that HCMV infection induced the mislocalization of nuclear lamins and that pUL50 and pUL53 play a role in this event. At late stages of infection, both lamin A/C and lamin B showed an irregular distribution on the nuclear rim, coincident with areas of pUL53 accumulation. No variations in the total amount of nuclear lamins could be detected, supporting the view that HCMV induces a qualitative, rather than a quantitative, alteration of these cellular components, as has been suggested previously for other herpesviruses. Interestingly, pUL53, in the absence of other viral products, localized diffusely in the nucleus, whilst the co-expression and interaction of pUL53 with its partner, pUL50, restored its nuclear rim localization in distinct patches, thus indicating that pUL50 is sufficient to induce the localization of pUL53 observed during virus infection. Importantly, analysis of the nuclear lamina in the presence of pUL50-pUL53 complexes at the nuclear boundary and in the absence of other viral products showed that the two viral proteins were sufficient to promote alterations of lamins, strongly resembling those observed during HCMV infection. These results suggest that pUL50 and pUL53 may play an important role in the exit of virions from the nucleus by inducing structural modifications of the nuclear lamina.
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Microbiology, University of Bologna, St Orsola General Hospital, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Camozzi
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Microbiology, University of Bologna, St Orsola General Hospital, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Pignatelli
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Microbiology, University of Bologna, St Orsola General Hospital, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Valvo
authors.affiliation: IGM-CNR, Unit of Bologna, c/o IOR, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lattanzi
authors.affiliation: IGM-CNR, Unit of Bologna, c/o IOR, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Capanni
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Microbiology, University of Bologna, St Orsola General Hospital, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Dal Monte
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Microbiology, University of Bologna, St Orsola General Hospital, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Landini
mesh_terms: D000818:Animals; D019556:COS Cells / Q000821:virology; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000378:metabolism / Q000472:pathogenicity*; D005347:Fibroblasts / Q000821:virology; D006801:Humans; D047468:Immunoprecipitation; D034882:Lamins / Q000378:metabolism; D008168:Lung / Q000166:cytology; D034881:Nuclear Lamina / Q000378:metabolism* / Q000821:virology*; D014764:Viral Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism
chemical_list: D034882:Lamins; D014764:Viral Proteins; C523758:pUL50 protein, cytomegalovirus; C523759:pUL53 protein, cytomegalovirus