Human cytomegalovirus UL76 induces chromosome aberrations

<p>Abstract</p> <p>Background</p> <p>Human cytomegalovirus (HCMV) is known to induce chromosome aberrations in infected cells, which can lead to congenital abnormalities in infected fetuses. HCMV UL76 belongs to a conserved protein family from herpesviruses. Some report...

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Main Authors: Wang Shang-Kwei, Duh Chang-Yih, Siew Voon-Kwan
Format: Article
Language:English
Published: BMC 2009-11-01
Series:Journal of Biomedical Science
Online Access:http://www.jbiomedsci.com/content/16/1/107
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spelling doaj-fdbf95b215de4206a9994732a3ef92782020-11-24T20:44:16ZengBMCJournal of Biomedical Science1021-77701423-01272009-11-0116110710.1186/1423-0127-16-107Human cytomegalovirus UL76 induces chromosome aberrationsWang Shang-KweiDuh Chang-YihSiew Voon-Kwan<p>Abstract</p> <p>Background</p> <p>Human cytomegalovirus (HCMV) is known to induce chromosome aberrations in infected cells, which can lead to congenital abnormalities in infected fetuses. HCMV UL76 belongs to a conserved protein family from herpesviruses. Some reported roles among UL76 family members include involvement in virulence determination, lytic replication, reactivation of latent virus, modulation of gene expression, induction of apoptosis, and perturbation of cell cycle progression, as well as potential nuclease activity. Previously, we have shown that stable expression of UL76 inhibits HCMV replication in glioblastoma cells.</p> <p>Methods</p> <p>To examine chromosomal integrity and the DNA damage signal γ-H2AX in cells constitutively expressing UL76, immunofluorescent cell staining and Western blotting were performed. The comet assay was employed to assess DNA breaks in cells transiently expressing UL76.</p> <p>Results</p> <p>We report that stably transfected cells expressing UL76 developed chromosome aberrations including micronuclei and misaligned chromosomes, lagging and bridging. In mitotic cells expressing UL76, aberrant spindles were increased compared to control cells. However, cells with supernumerary centrosomes were marginally increased in UL76-expressing cells relative to control cells. We further demonstrated that UL76-expressing cells activated the DNA damage signal γ-H2AX and caused foci formation in nuclei. In addition, the number of cells with DNA breaks increased in proportion to UL76 protein levels.</p> <p>Conclusion</p> <p>Our findings suggest that the virus-associated protein UL76 induces DNA damage and the accumulation of chromosome aberrations.</p> http://www.jbiomedsci.com/content/16/1/107
collection DOAJ
language English
format Article
sources DOAJ
author Wang Shang-Kwei
Duh Chang-Yih
Siew Voon-Kwan
spellingShingle Wang Shang-Kwei
Duh Chang-Yih
Siew Voon-Kwan
Human cytomegalovirus UL76 induces chromosome aberrations
Journal of Biomedical Science
author_facet Wang Shang-Kwei
Duh Chang-Yih
Siew Voon-Kwan
author_sort Wang Shang-Kwei
title Human cytomegalovirus UL76 induces chromosome aberrations
title_short Human cytomegalovirus UL76 induces chromosome aberrations
title_full Human cytomegalovirus UL76 induces chromosome aberrations
title_fullStr Human cytomegalovirus UL76 induces chromosome aberrations
title_full_unstemmed Human cytomegalovirus UL76 induces chromosome aberrations
title_sort human cytomegalovirus ul76 induces chromosome aberrations
publisher BMC
series Journal of Biomedical Science
issn 1021-7770
1423-0127
publishDate 2009-11-01
description <p>Abstract</p> <p>Background</p> <p>Human cytomegalovirus (HCMV) is known to induce chromosome aberrations in infected cells, which can lead to congenital abnormalities in infected fetuses. HCMV UL76 belongs to a conserved protein family from herpesviruses. Some reported roles among UL76 family members include involvement in virulence determination, lytic replication, reactivation of latent virus, modulation of gene expression, induction of apoptosis, and perturbation of cell cycle progression, as well as potential nuclease activity. Previously, we have shown that stable expression of UL76 inhibits HCMV replication in glioblastoma cells.</p> <p>Methods</p> <p>To examine chromosomal integrity and the DNA damage signal γ-H2AX in cells constitutively expressing UL76, immunofluorescent cell staining and Western blotting were performed. The comet assay was employed to assess DNA breaks in cells transiently expressing UL76.</p> <p>Results</p> <p>We report that stably transfected cells expressing UL76 developed chromosome aberrations including micronuclei and misaligned chromosomes, lagging and bridging. In mitotic cells expressing UL76, aberrant spindles were increased compared to control cells. However, cells with supernumerary centrosomes were marginally increased in UL76-expressing cells relative to control cells. We further demonstrated that UL76-expressing cells activated the DNA damage signal γ-H2AX and caused foci formation in nuclei. In addition, the number of cells with DNA breaks increased in proportion to UL76 protein levels.</p> <p>Conclusion</p> <p>Our findings suggest that the virus-associated protein UL76 induces DNA damage and the accumulation of chromosome aberrations.</p>
url http://www.jbiomedsci.com/content/16/1/107
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AT duhchangyih humancytomegalovirusul76induceschromosomeaberrations
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