Restriction of human herpesvirus 6B replication by p53

Abstract

Human herpesvirus 6B (HHV-6B) induces significant accumulation of p53 in both the nucleus and cytoplasm during infection. Activation of p53 by DNA damage is known to induce either growth arrest or apoptosis; nevertheless, HHV-6B-infected cells are arrested in their cell cycle independently of p53, and only a minor fraction of the infected cells undergoes apoptosis. Using pifithrin-α, a p53 inhibitor, and p53-null cells, this study showed that infected epithelial cells accumulated viral transcripts and proteins to a significantly higher degree in the absence of active p53. Moreover, HHV-6B-induced cytopathic effects were greatly enhanced in the absence of p53. This suggests that, in epithelial cells, some of the functions of p53 leading to cell-cycle arrest and apoptosis are restrained by HHV-6B infection, whereas other cellular defences, causing inhibition of virus transcription, are partially retained.

p53 Regulates Toll-Like Receptor 3 Expression and Function in Human Epithelial Cell Lines

“…p53 has been implicated in the innate response to pathogens (30,31), and while TLRs are well known for mediating the recognition and response to microbial products, the relationship between p53 and TLRs is largely unexplored. To assess the involvement of p53 in TLRs' response to PAMPs, we stimulated HCT116 p53 ϩ/ϩ and p53 Ϫ/Ϫ cells with various TLR ligands, such as PGN, poly(I-C), LPS, B-DNA, and R848, and we assayed the promoter activity of IL-8, a general downstream cytokine of TLRs, in cells treated with these TLR ligands.…”

“…Inactivation of p53 protein can be induced by some viruses implicated in the development of cancer (6,31) as one of the viral mechanisms to inhibit apoptosis and prolong the survival of the virus. However, viruses with no tumorigenic potential and double-stranded RNA (dsRNA) have also been shown to downregulate p53 (14,25), suggesting the importance of p53 in host response to viruses.…”

Herpesvirus type 7 infection may play an important role in individuals with a genetic profile of susceptibility to Graves' disease

“…During infection, HHV-6B induces significant accumulation of p53 in both the nucleus and cytoplasm, and determines phosphorylation of p53 at Ser392 (13)(14)(15). TP53 restricts the production of HHV-6B mRNAs and proteins, which inhibits viral replication and diminishes the cytopathic effects of the virus (16). On the other hand, TP53 may also participate in the autoimmune process since DNA damage and apoptosis may be associated with autoimmune thyroid disease.…”

Involvement of Human Herpesvirus-6 Variant B in Classic Hodgkin's Lymphoma via DR7 Oncoprotein

“…Human papillomavirus 16 and 18 oncoproteins E6, SV40 oncoprotein large T antigen, and adenovirus E1B 55-kDa protein have all been shown to interact with p53 protein, inhibiting its control of cell cycle arrest after DNA damage. The finding that DR7B was able to bind to human p53 suggests that this interaction may induce or participate in lymphomagenesis, considering the fact that HHV-6 is able to retain p53 within the cytoplasm, thus protecting infected cells from apoptosis (40,41). This leads to p53 accumulation and upregulation in the presence of HHV-6 (42).…”