In:
The Journal of Immunology, The American Association of Immunologists, Vol. 186, No. 1_Supplement ( 2011-04-01), p. 154.38-154.38
Abstract:
Human herpesvirus 6 is an important immunosuppressive and immunomodulatory virus which infects immune cells and strongly suppresses the proliferation of infected cells. However, the mechanisms responsible for the regulation and suppression mediated by HHV-6 are still unknown. In this study, we examined the ability of HHV-6A to manipulate cell cycle progression in the infected cells and explored the potential molecular mechanisms. We demonstrated that infection with HHV-6A imposed a growth-inhibitory effect on HSB-2 cells by inducing cell cycle arrest at G2/M phase. We then showed that the activity of Cdc2-cyclinB1 complex was significantly decreased in HHV-6A infected HSB-2 cells. Furthermore, we found that inactivation of Cdc2-cyclinB1 in infected cells was through the inhibitory Tyr15 phosphorylation resulting from the elevated Wee1 expression and inactivated Cdc25C; Meanwhile, the reduction of Cdc2-cyclinB1 activity in infected cells was also partly due to the increased expression of cell cycle regulatory molecule p21 in a p53-dependent manner. In addition, HHV-6A infection activated the DNA damage checkpoint kinases, Chk2 and Chk1. Our data suggest that HHV-6A infection induces G2/M arrest in infected T cells via various regulatory mechanisms. These results demonstrate potential mechanisms involved in immune suppression and modulation mediated by HHV-6 infection, and provide new insights relevant to the development of novel vaccines and immunotherapeutic approaches.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.186.Supp.154.38
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2011
detail.hit.zdb_id:
1475085-5
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