title: The absence of p53 during Human Cytomegalovirus infection leads to decreased UL53 expression, disrupting UL50 localization to the inner nuclear membrane, and thereby inhibiting capsid nuclear egress.
abstract: Our electron microscopy study (Kuan et al., 2016) found HCMV nuclear capsid egress was significantly reduced in p53 knockout cells (p53KOs), correlating with inhibited formation of infoldings of the inner nuclear membrane (IINMs). Molecular examination of these phenomena has found p53KOs expressed UL97 and phosphorylated lamins, however the lamina failed to remodel. The nuclear egress complex (NEC) protein UL50 was expressed in almost all cells. UL50 re-localized to the inner nuclear membrane (INM) in ~90% of wt cells, but only ~35% of p53KOs. UL53 expression was significantly reduced in p53KOs, and cells lacking UL50 nuclear staining, expressed no UL53. Re-introduction of p53 into p53KOs largely recovered UL53 positivity and UL50 nuclear re-localization. Nuclear rim located UL50/53 puncta, which co-localized with the major capsid protein, were largely absent in p53KOs. We believe these puncta were IINMs. In the absence of p53, UL53 expression was inhibited, disrupting formation of the NEC/IINMs, and reducing functional virion secretion.
authors: Department of Biological Sciences and Center for Reproductive Biology, University of Idaho, Moscow, ID, USA.
authors: Man I
authors: MI
authors: Kuan
authors: Department of Biological Sciences and Center for Reproductive Biology, University of Idaho, Moscow, ID, USA.
authors: John M
authors: JM
authors: O'Dowd
authors: Department of Biological Sciences and Center for Reproductive Biology, University of Idaho, Moscow, ID, USA. Electronic address: lfort@uidaho.edu.
authors: Elizabeth A
authors: EA
authors: Fortunato
mesh_terms: D036022:Capsid Proteins / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D055786:Gene Knockout Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins
keywords: Confocal microscopy; Human Cytomegalovirus; Infoldings of inner nuclear membrane; Nuclear egress complex; P53; UL50 and UL53