Viral oncoapoptosis of human tumor cells

Aubert, Martine; Blaho, John A.

doi:10.1038/sj.gt.3302004

Cited by 26 publications

(35 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among other cell death-related mechanisms, autophagy seems to inhibit HSV-1 replication (Pei et al, 2011), and the anti-autophagic effect of HSV-1 ICP34.5 has been well described Orvedahl et al, 2007). Additionally, HSV-1 infection induces autophagy in some cells including cell death mechanisms appears to be dependent on differences in cell type (Aubert & Blaho, 2003;English et al, 2009;Galvan & Roizman, 1998;McFarlane et al, 2011;Nguyen et al, 2005), cellular factors may be important for HSV-1-induced cell death and viral replication. Thus, in this study, the effects of axin expression were investigated in terms of HSV-1 replication and virus-mediated cell death to analyse the influence of host factors during HSV-1 infection.…”

Section: Introductionmentioning

confidence: 99%

Axin expression enhances herpes simplex virus type 1 replication by inhibiting virus-mediated cell death in L929 cells

Choi

Kim

Jho

et al. 2013

Journal of General Virology

View full text Add to dashboard Cite

Herpes simplex virus type 1 (HSV-1) replicates in various cell types and induces early cell death, which limits viral replication in certain cell types. Axin is a scaffolding protein that regulates Wnt signalling and participates in various cellular events, including cellular proliferation and cell death. The effects of axin expression on HSV-1 infection were investigated based on our initial observation that Wnt3a treatment or axin knockdown reduced HSV-1 replication. L929 cells expressed the axin protein in a doxycycline-inducible manner (L-axin) and enhanced HSV-1 replication in comparison to control cells (L-EV). HSV-1 infection induced cell death as early as 6 h after infection through the necrotic pathway and required de novo protein synthesis in L929 cells. Subsequent analysis of viral protein expression suggested that axin expression led to suppression of HSV-1-induced premature cell death, resulting in increased late gene expression. In analysis of axin deletion mutants, the regulators of the G-protein signalling (RGS) domain were involved in the axin-mediated enhancement of viral replication and reduction in cell death. These results suggest that viral replication enhancement might be mediated by the axin RGS domain.

show abstract

Section: Introductionmentioning

confidence: 99%

Axin expression enhances herpes simplex virus type 1 replication by inhibiting virus-mediated cell death in L929 cells

Choi

Kim

Jho

et al. 2013

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…In addition, the HSV-1 latency-associated transcript has a pro-survival function as this RNA transcript can inhibit apoptosis (Ghiasi et al, 2002;Li et al, 2010; Perng et al, 2000;Thompson & Sawtell, 2001). The extent of apoptosis observed following HSV-1 infection is cell-type-dependent, indicating that HSV-1-induced apoptosis is regulated by different cellular factors such as caspases, Bcl-2 family members and nuclear factor kB (Ahmed et al, 2002;Asano et al, 2000;Aubert & Blaho, 2003 In addition to apoptosis, cathepsins mediate or regulate the cellular lysosomal degradation pathway called autophagy (Uchiyama, 2001). Autophagy is a highly conserved mechanism, which plays an important role, among others, in recycling nutrients and energy, and degrading unwanted cytoplasmic constituents.…”

mentioning

confidence: 99%

Cathepsins are involved in virus-induced cell death in ICP4 and Us3 deletion mutant herpes simplex virus type 1-infected monocytic cells

Peri

Nuutila

Vuorinen

et al. 2010

Journal of General Virology

View full text Add to dashboard Cite

We have studied cell death and its mechanisms in herpes simplex virus type 1 (HSV-1)-infected monocytic cells. The HSV-1 ICP4 and Us3 deletion mutant, d120 caused both apoptosis and necroptosis in d120-infected monocytic cells. At a late time point of infection the number of apoptotic cells was increased significantly in d120-infected cells when compared with uninfected or parental HSV-1 (KOS)-infected cells. Necroptosis inhibitor treatment increased the number of viable cells among the d120-infected cells, indicating that cell death in d120-infected cells was, in part, because of necroptosis. Moreover, lysosomal membrane permeabilization and cathepsin B and H activities were increased significantly in d120-infected cells. Inhibition of cathepsin B and S activities with specific cathepsin inhibitors led to increased cell viability, and inhibition of cathepsin L activity resulted in a decreased number of apoptotic cells. This indicates that cathepsins B, L and S may act as cell-death mediators in d120-infected monocytic cells. In addition, caspase 3 activity was increased significantly in d120-infected cells. However, the caspase 3 inhibitor treatment did not decrease the number of apoptotic cells. In contrast, inhibition of cathepsin L activity by cathepsin L-specific inhibitor clearly decreased caspase 3 activity and the number of apoptotic cells in d120-infected cells. This might suggest that, in d120-infected monocytic cells, cathepsin L activates caspase 3 and thus mediates d120-induced apoptosis. Taken together, these findings suggest that d120-induced cell death is both apoptotic and necroptotic. INTRODUCTIONHerpes simplex virus type 1 (HSV-1) is a common pathogen that replicates in a variety of cell types during acute infection . After lytic infection HSV-1 remains latent in the neurons of its host for life and can reactivate to cause lesions at or near the initial site of infection. Like other herpesviruses, HSV-1 expresses a large number of enzymes involved in nucleic acid metabolism, DNA synthesis and the processing of proteins. Productive viral infection is accompanied by inevitable cell destruction. HSV-1 has several strategies to combat the responses of the infected host, among them the prevention of the blocking protein kinase R-mediated shut-off of host protein synthesis (He et al., 1997), having a latent form of infection with no protein expression , blocking presentation of antigenic peptides on the cell surface (Fruh et al., 1995;Hill et al., 1995) and blocking apoptosis (Galvan & Roizman, 1998;Leopardi & Roizman, 1996;Leopardi et al., 1997).HSV-1 entry triggers the induction of apoptosis during the early stage of infection (Aubert & Blaho, 1999;Koyama & Adachi, 1997). However, HSV-1 is able to block apoptosis at multiple stages of infection to prevent the host cell from dying prematurely (Aubert & Blaho, 1999;Galvan & Roizman, 1998;Koyama & Miwa, 1997). For example, the late protein kinase Us3 contributes to blocking HSV-1-induced apoptosis (Leopardi et al., 1997;Munger & Roizman, 2001). Other...

show abstract

“…15 However, different cancer cell lines have different levels of susceptibility to the virus, 20 and therefore it is important to optimize its effects. We used cells from human breast carcinomas to test the hypothesis that combining HSV-1 infection with a caspase inhibitor would result in increased killing of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…HSV-1 infection triggers apoptosis by both caspase-dependent and -independent pathways, 19 but the expression of viral proteins 3-6 h post-infection (hpi) blocks cellular death and allows for efficient viral replication. [19][20][21][22][23] HSV-1 expresses multiple proteins that act to prevent cellular apoptosis including infected cell protein 4 (ICP4), ICP27, ICP34.5, U S 3 and U s 5 kinase, and gJ. 21,22,24,25 Others have therefore proposed that anti-apoptosis drugs might allow infected tumor cells to resist apoptosis, at least temporarily, thus allowing greater replication of the virus and a stronger anti-tumor effect in the long term.…”

Section: Introductionmentioning

confidence: 99%

Effect of a caspase inhibitor, zVADfmk, on the inhibition of breast cancer cells by herpes simplex virus type 1

Wood

Shillitoe

2011

Cancer Gene Ther

View full text Add to dashboard Cite

The oncolytic effects of herpes simplex virus-1 (HSV-1) are limited, possibly because of premature death of infected cells by apoptosis, which limits the amount of progeny virus that is produced. It has been proposed that inhibition of apoptosis in infected tumor cells would allow increased viral persistence, replication and therapeutic effect. To test this hypothesis, we infected monocyte chemoattractant factor-7 (MCF-7) and MDA-MB-231 breast cancer cells with HSV-1 strain 17 þ and 17Dg34.5 in the presence or absence of N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVADfmk), a pan-caspase inhibitor. At low doses of HSV-1 strain 17 þ and 17Dg34.5, the growth of MCF-7 cells was reduced to 37% or 42%, respectively, of uninfected cells. However, when cells were infected in the presence of zVADfmk, cell growth was further reduced to 24 and 33%. Similar results were seen in MDA-MB-231 cells. Cells treated with zVADfmk contained roughly 10 times more infectious viral particles than cells infected without zVADfmk, as shown by both plaque-forming and quantitative polymerase chain reaction assays. To model the situation within an infected tumor, supernatant fluids were collected from infected and non-infected cell cultures and then passed to non-infected cells. In the presence of zVADfmk, the cell growth inhibitory effect became stronger with repeated passages and was attributed to viral replication, because it could be prevented by anti-HSV antibody. These results suggest that caspases represent a novel target for drugs that increase the therapeutic efficacy of oncolytic herpes viruses against breast cancer.

show abstract

Viral oncoapoptosis of human tumor cells

Cited by 26 publications

References 75 publications

Axin expression enhances herpes simplex virus type 1 replication by inhibiting virus-mediated cell death in L929 cells

Axin expression enhances herpes simplex virus type 1 replication by inhibiting virus-mediated cell death in L929 cells

Cathepsins are involved in virus-induced cell death in ICP4 and Us3 deletion mutant herpes simplex virus type 1-infected monocytic cells

Effect of a caspase inhibitor, zVADfmk, on the inhibition of breast cancer cells by herpes simplex virus type 1

Contact Info

Product

Resources

About