WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress [Virus-Cell Interactions]

Publication Date:
2018-04-14
Publisher:
The American Society for Microbiology (ASM)
Print ISSN:
0022-538X
Electronic ISSN:
1098-5514
Topics:
Medicine
Published by:
http://www.asm.org/
_version_ 1836398893324042240
autor Yang, B., Liu, X.-J., Yao, Y., Jiang, X., Wang, X.-Z., Yang, H., Sun, J.-Y., Miao, Y., Wang, W., Huang, Z.-L., Wang, Y., Tang, Q., Rayner, S., Britt, W. J., McVoy, M. A., Luo, M.-H., Zhao, F.
beschreibung WD repeat-containing protein 5 (WDR5) is essential for assembling the VISA-associated complex to induce a type I interferon antiviral response to Sendai virus infection. However, the roles of WDR5 in DNA virus infections are not well described. Here, we report that human cytomegalovirus exploits WDR5 to facilitate capsid nuclear egress. Overexpression of WDR5 in fibroblasts slightly enhanced the infectious virus yield. However, WDR5 knockdown dramatically reduced infectious virus titers with only a small decrease in viral genome replication or gene expression. Further investigation of late steps of viral replication found that WDR5 knockdown significantly impaired formation of the viral nuclear egress complex and induced substantially fewer infoldings of the inner nuclear membrane. In addition, fewer capsids were associated with these infoldings, and there were fewer capsids in the cytoplasm. Restoration of WDR5 partially reversed these effects. These results suggest that WDR5 knockdown impairs the nuclear egress of capsids, which in turn decreases virus titers. These findings reveal an important role for a host factor whose function(s) is usurped by a viral pathogen to promote efficient replication. Thus, WDR5 represents an interesting regulatory mechanism and a potential antiviral target. IMPORTANCE Human cytomegalovirus (HCMV) has a large (~235-kb) genome with over 170 open reading frames and exploits numerous cellular factors to facilitate its replication. HCMV infection increases protein levels of WD repeat-containing protein 5 (WDR5) during infection, overexpression of WDR5 enhances viral replication, and knockdown of WDR5 dramatically attenuates viral replication. Our results indicate that WDR5 promotes the nuclear egress of viral capsids, the depletion of WDR5 resulting in a significant decrease in production of infectious virions. This is the first report that WDR5 favors HCMV, a DNA virus, replication and highlights a novel target for antiviral therapy.
citation_standardnr 6234897
datenlieferant ipn_articles
feed_id 2375
feed_publisher The American Society for Microbiology (ASM)
feed_publisher_url http://www.asm.org/
insertion_date 2018-04-14
journaleissn 1098-5514
journalissn 0022-538X
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Society for Microbiology (ASM)
quelle Journal of Virology
relation http://jvi.asm.org/cgi/content/short/92/9/e00207-18?rss=1
search_space articles
shingle_author_1 Yang, B., Liu, X.-J., Yao, Y., Jiang, X., Wang, X.-Z., Yang, H., Sun, J.-Y., Miao, Y., Wang, W., Huang, Z.-L., Wang, Y., Tang, Q., Rayner, S., Britt, W. J., McVoy, M. A., Luo, M.-H., Zhao, F.
shingle_author_2 Yang, B., Liu, X.-J., Yao, Y., Jiang, X., Wang, X.-Z., Yang, H., Sun, J.-Y., Miao, Y., Wang, W., Huang, Z.-L., Wang, Y., Tang, Q., Rayner, S., Britt, W. J., McVoy, M. A., Luo, M.-H., Zhao, F.
shingle_author_3 Yang, B., Liu, X.-J., Yao, Y., Jiang, X., Wang, X.-Z., Yang, H., Sun, J.-Y., Miao, Y., Wang, W., Huang, Z.-L., Wang, Y., Tang, Q., Rayner, S., Britt, W. J., McVoy, M. A., Luo, M.-H., Zhao, F.
shingle_author_4 Yang, B., Liu, X.-J., Yao, Y., Jiang, X., Wang, X.-Z., Yang, H., Sun, J.-Y., Miao, Y., Wang, W., Huang, Z.-L., Wang, Y., Tang, Q., Rayner, S., Britt, W. J., McVoy, M. A., Luo, M.-H., Zhao, F.
shingle_catch_all_1 WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress [Virus-Cell Interactions]
WD repeat-containing protein 5 (WDR5) is essential for assembling the VISA-associated complex to induce a type I interferon antiviral response to Sendai virus infection. However, the roles of WDR5 in DNA virus infections are not well described. Here, we report that human cytomegalovirus exploits WDR5 to facilitate capsid nuclear egress. Overexpression of WDR5 in fibroblasts slightly enhanced the infectious virus yield. However, WDR5 knockdown dramatically reduced infectious virus titers with only a small decrease in viral genome replication or gene expression. Further investigation of late steps of viral replication found that WDR5 knockdown significantly impaired formation of the viral nuclear egress complex and induced substantially fewer infoldings of the inner nuclear membrane. In addition, fewer capsids were associated with these infoldings, and there were fewer capsids in the cytoplasm. Restoration of WDR5 partially reversed these effects. These results suggest that WDR5 knockdown impairs the nuclear egress of capsids, which in turn decreases virus titers. These findings reveal an important role for a host factor whose function(s) is usurped by a viral pathogen to promote efficient replication. Thus, WDR5 represents an interesting regulatory mechanism and a potential antiviral target. IMPORTANCE Human cytomegalovirus (HCMV) has a large (~235-kb) genome with over 170 open reading frames and exploits numerous cellular factors to facilitate its replication. HCMV infection increases protein levels of WD repeat-containing protein 5 (WDR5) during infection, overexpression of WDR5 enhances viral replication, and knockdown of WDR5 dramatically attenuates viral replication. Our results indicate that WDR5 promotes the nuclear egress of viral capsids, the depletion of WDR5 resulting in a significant decrease in production of infectious virions. This is the first report that WDR5 favors HCMV, a DNA virus, replication and highlights a novel target for antiviral therapy.
Yang, B., Liu, X.-J., Yao, Y., Jiang, X., Wang, X.-Z., Yang, H., Sun, J.-Y., Miao, Y., Wang, W., Huang, Z.-L., Wang, Y., Tang, Q., Rayner, S., Britt, W. J., McVoy, M. A., Luo, M.-H., Zhao, F.
The American Society for Microbiology (ASM)
0022-538X
0022538X
1098-5514
10985514
shingle_catch_all_2 WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress [Virus-Cell Interactions]
WD repeat-containing protein 5 (WDR5) is essential for assembling the VISA-associated complex to induce a type I interferon antiviral response to Sendai virus infection. However, the roles of WDR5 in DNA virus infections are not well described. Here, we report that human cytomegalovirus exploits WDR5 to facilitate capsid nuclear egress. Overexpression of WDR5 in fibroblasts slightly enhanced the infectious virus yield. However, WDR5 knockdown dramatically reduced infectious virus titers with only a small decrease in viral genome replication or gene expression. Further investigation of late steps of viral replication found that WDR5 knockdown significantly impaired formation of the viral nuclear egress complex and induced substantially fewer infoldings of the inner nuclear membrane. In addition, fewer capsids were associated with these infoldings, and there were fewer capsids in the cytoplasm. Restoration of WDR5 partially reversed these effects. These results suggest that WDR5 knockdown impairs the nuclear egress of capsids, which in turn decreases virus titers. These findings reveal an important role for a host factor whose function(s) is usurped by a viral pathogen to promote efficient replication. Thus, WDR5 represents an interesting regulatory mechanism and a potential antiviral target. IMPORTANCE Human cytomegalovirus (HCMV) has a large (~235-kb) genome with over 170 open reading frames and exploits numerous cellular factors to facilitate its replication. HCMV infection increases protein levels of WD repeat-containing protein 5 (WDR5) during infection, overexpression of WDR5 enhances viral replication, and knockdown of WDR5 dramatically attenuates viral replication. Our results indicate that WDR5 promotes the nuclear egress of viral capsids, the depletion of WDR5 resulting in a significant decrease in production of infectious virions. This is the first report that WDR5 favors HCMV, a DNA virus, replication and highlights a novel target for antiviral therapy.
Yang, B., Liu, X.-J., Yao, Y., Jiang, X., Wang, X.-Z., Yang, H., Sun, J.-Y., Miao, Y., Wang, W., Huang, Z.-L., Wang, Y., Tang, Q., Rayner, S., Britt, W. J., McVoy, M. A., Luo, M.-H., Zhao, F.
The American Society for Microbiology (ASM)
0022-538X
0022538X
1098-5514
10985514
shingle_catch_all_3 WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress [Virus-Cell Interactions]
WD repeat-containing protein 5 (WDR5) is essential for assembling the VISA-associated complex to induce a type I interferon antiviral response to Sendai virus infection. However, the roles of WDR5 in DNA virus infections are not well described. Here, we report that human cytomegalovirus exploits WDR5 to facilitate capsid nuclear egress. Overexpression of WDR5 in fibroblasts slightly enhanced the infectious virus yield. However, WDR5 knockdown dramatically reduced infectious virus titers with only a small decrease in viral genome replication or gene expression. Further investigation of late steps of viral replication found that WDR5 knockdown significantly impaired formation of the viral nuclear egress complex and induced substantially fewer infoldings of the inner nuclear membrane. In addition, fewer capsids were associated with these infoldings, and there were fewer capsids in the cytoplasm. Restoration of WDR5 partially reversed these effects. These results suggest that WDR5 knockdown impairs the nuclear egress of capsids, which in turn decreases virus titers. These findings reveal an important role for a host factor whose function(s) is usurped by a viral pathogen to promote efficient replication. Thus, WDR5 represents an interesting regulatory mechanism and a potential antiviral target. IMPORTANCE Human cytomegalovirus (HCMV) has a large (~235-kb) genome with over 170 open reading frames and exploits numerous cellular factors to facilitate its replication. HCMV infection increases protein levels of WD repeat-containing protein 5 (WDR5) during infection, overexpression of WDR5 enhances viral replication, and knockdown of WDR5 dramatically attenuates viral replication. Our results indicate that WDR5 promotes the nuclear egress of viral capsids, the depletion of WDR5 resulting in a significant decrease in production of infectious virions. This is the first report that WDR5 favors HCMV, a DNA virus, replication and highlights a novel target for antiviral therapy.
Yang, B., Liu, X.-J., Yao, Y., Jiang, X., Wang, X.-Z., Yang, H., Sun, J.-Y., Miao, Y., Wang, W., Huang, Z.-L., Wang, Y., Tang, Q., Rayner, S., Britt, W. J., McVoy, M. A., Luo, M.-H., Zhao, F.
The American Society for Microbiology (ASM)
0022-538X
0022538X
1098-5514
10985514
shingle_catch_all_4 WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress [Virus-Cell Interactions]
WD repeat-containing protein 5 (WDR5) is essential for assembling the VISA-associated complex to induce a type I interferon antiviral response to Sendai virus infection. However, the roles of WDR5 in DNA virus infections are not well described. Here, we report that human cytomegalovirus exploits WDR5 to facilitate capsid nuclear egress. Overexpression of WDR5 in fibroblasts slightly enhanced the infectious virus yield. However, WDR5 knockdown dramatically reduced infectious virus titers with only a small decrease in viral genome replication or gene expression. Further investigation of late steps of viral replication found that WDR5 knockdown significantly impaired formation of the viral nuclear egress complex and induced substantially fewer infoldings of the inner nuclear membrane. In addition, fewer capsids were associated with these infoldings, and there were fewer capsids in the cytoplasm. Restoration of WDR5 partially reversed these effects. These results suggest that WDR5 knockdown impairs the nuclear egress of capsids, which in turn decreases virus titers. These findings reveal an important role for a host factor whose function(s) is usurped by a viral pathogen to promote efficient replication. Thus, WDR5 represents an interesting regulatory mechanism and a potential antiviral target. IMPORTANCE Human cytomegalovirus (HCMV) has a large (~235-kb) genome with over 170 open reading frames and exploits numerous cellular factors to facilitate its replication. HCMV infection increases protein levels of WD repeat-containing protein 5 (WDR5) during infection, overexpression of WDR5 enhances viral replication, and knockdown of WDR5 dramatically attenuates viral replication. Our results indicate that WDR5 promotes the nuclear egress of viral capsids, the depletion of WDR5 resulting in a significant decrease in production of infectious virions. This is the first report that WDR5 favors HCMV, a DNA virus, replication and highlights a novel target for antiviral therapy.
Yang, B., Liu, X.-J., Yao, Y., Jiang, X., Wang, X.-Z., Yang, H., Sun, J.-Y., Miao, Y., Wang, W., Huang, Z.-L., Wang, Y., Tang, Q., Rayner, S., Britt, W. J., McVoy, M. A., Luo, M.-H., Zhao, F.
The American Society for Microbiology (ASM)
0022-538X
0022538X
1098-5514
10985514
shingle_title_1 WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress [Virus-Cell Interactions]
shingle_title_2 WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress [Virus-Cell Interactions]
shingle_title_3 WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress [Virus-Cell Interactions]
shingle_title_4 WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress [Virus-Cell Interactions]
timestamp 2025-06-30T23:34:18.898Z
titel WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress [Virus-Cell Interactions]
titel_suche WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress [Virus-Cell Interactions]
topic WW-YZ
uid ipn_articles_6234897