title: Human Cytomegalovirus nuclear egress and secondary envelopment are negatively affected in the absence of cellular p53.
abstract: Human Cytomegalovirus (HCMV) infection is compromised in cells lacking p53, a transcription factor that mediates cellular stress responses. In this study we have investigated compromised functional virion production in cells with p53 knocked out (p53KOs). Infectious center assays found most p53KOs released functional virions. Analysis of electron micrographs revealed modestly decreased capsid production in infected p53KOs compared to wt. Substantially fewer p53KOs displayed HCMV-induced infoldings of the inner nuclear membrane (IINMs). In p53KOs, fewer capsids were found in IINMs and in the cytoplasm. The deficit in virus-induced membrane remodeling within the nucleus of p53KOs was mirrored in the cytoplasm, with a disproportionately smaller number of capsids re-enveloped. Reintroduction of p53 substantially recovered these deficits. Overall, the absence of p53 contributed to inhibition of the formation and function of IINMs and re-envelopment of the reduced number of capsids able to reach the cytoplasm.
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.
authors: Kamila
authors: K
authors: Chughtai
authors: Department of Biological Sciences and Center for Reproductive Biology, University of Idaho, Moscow, ID, USA.
authors: Ian
authors: I
authors: Hayman
authors: Department of Biological Sciences and Center for Reproductive Biology, University of Idaho, Moscow, ID, USA.
authors: Celeste J
authors: CJ
authors: Brown
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: D002213:Capsid / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D055786:Gene Knockout Techniques; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000378:metabolism; D019065:Virus Assembly; D057074:Virus Release; D014779:Virus Replication; D017201:Virus Shedding
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: Capsids; Human Cytomegalovirus; Infoldings of the inner nuclear membrane (IINM); Nuclear egress; Secondary envelopment; Transmission electron microscopy (TEM); p53