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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. -- Highlights: •The majority of p53KO cells release fewer functional virions than wt cells. •Nucleocapsids do not efficiently exit the nucleus in p53KO cells. •Infoldings of the inner nuclear membrane are not efficiently formed in p53KO cells. •Cytoplasmic capsids are not efficiently re-enveloped in p53KO cells. •Reintroduction of p53 largely ameliorates these phenotypes.

Authors:
; ; ;
Publication Date:
OSTI Identifier:
22692219
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 497; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CYTOPLASM; INHIBITION; MEMBRANES; PHENOTYPE; TRANSCRIPTION; TRANSCRIPTION FACTORS; TRANSMISSION ELECTRON MICROSCOPY; VIRUSES

Citation Formats

Kuan, Man I, O’Dowd, John M., Chughtai, Kamila, and Ha. Human Cytomegalovirus nuclear egress and secondary envelopment are negatively affected in the absence of cellular p53. United States: N. p., 2016. Web. doi:10.1016/J.VIROL.2016.07.021.
Kuan, Man I, O’Dowd, John M., Chughtai, Kamila, & Ha. Human Cytomegalovirus nuclear egress and secondary envelopment are negatively affected in the absence of cellular p53. United States. doi:10.1016/J.VIROL.2016.07.021.
Kuan, Man I, O’Dowd, John M., Chughtai, Kamila, and Ha. Sat . "Human Cytomegalovirus nuclear egress and secondary envelopment are negatively affected in the absence of cellular p53". United States. doi:10.1016/J.VIROL.2016.07.021.
@article{osti_22692219,
title = {Human Cytomegalovirus nuclear egress and secondary envelopment are negatively affected in the absence of cellular p53},
author = {Kuan, Man I and O’Dowd, John M. and Chughtai, Kamila and Ha},
abstractNote = {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. -- Highlights: •The majority of p53KO cells release fewer functional virions than wt cells. •Nucleocapsids do not efficiently exit the nucleus in p53KO cells. •Infoldings of the inner nuclear membrane are not efficiently formed in p53KO cells. •Cytoplasmic capsids are not efficiently re-enveloped in p53KO cells. •Reintroduction of p53 largely ameliorates these phenotypes.},
doi = {10.1016/J.VIROL.2016.07.021},
journal = {Virology},
issn = {0042-6822},
number = ,
volume = 497,
place = {United States},
year = {2016},
month = {10}
}