Disruption of the p53–p21 pathway inhibits efficiency of the lytic-replication cycle of herpes simplex virus type 2 (HSV-2)

Zhou, Qi; Zhu, Meng; Zhang, Hao; Yi, Tao; Klena, John D.; Peng, Yiru

doi:10.1016/j.virusres.2012.07.011

Cited by 4 publications

(5 citation statements)

References 49 publications

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“…Our results are also in the same range (i.e. less than a log difference) observed by others in recent studies analyzing the impact of cellular proteins on HSV or HIV proliferation [55], [56], [57], [58], [59], [60], [61]. Multi-log inhibitions where therefore not expected in the present study but it does naturally make it more difficult to ascribe a functional role to present host proteins.…”

Section: Discussionsupporting

confidence: 90%

Analysis of Virion-Incorporated Host Proteins Required for Herpes Simplex Virus Type 1 Infection through a RNA Interference Screen

et al. 2013

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Viruses are strictly dependent on cells to propagate and many incorporate host proteins in their viral particles, but the significance of this incorporation is poorly understood. Recently, we performed the first comprehensive characterization of the mature herpes simplex virus type 1 (HSV-1) in which up to 49 distinct cellular proteins were identified by mass spectrometry. In the present study, we sought to identify if these cellular factors are relevant for the HSV-1 life cycle. To this end, we performed a small interfering RNA functional screen and found that 15 of these host proteins altered HSV-1 proliferation in cell culture, without any significant effect on cell viability. Moreover, the siRNA used had no negative consequences for Adenovirus type 5 propagation (with one exception) indicating that the modulation was specific for HSV-1 and not merely due to unhealthy cells. The positive host proteins include several Rab GTPases and other intracellular transport components as well as proteins involved in signal transduction, gene regulation and immunity. Remarkably, in most cases when virions were depleted for one of the above proteins, they replicated more poorly in subsequent infections in wild type cells. This highlights for the first time that both the cellular and virion-associated pools of many of these proteins actively contribute to viral propagation. Altogether, these findings underscore the power and biological relevance of combining proteomics and RNA interference to identify novel host-pathogen interactions.

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Section: Discussionsupporting

confidence: 90%

Analysis of Virion-Incorporated Host Proteins Required for Herpes Simplex Virus Type 1 Infection through a RNA Interference Screen

et al. 2013

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“…Zhou et al . have shown that HSV replication is inhibited due the disruption of p53-p21 pathway, where the knockdown of p53 or p21 resulted in a significant reduction of HSV production 32 . Activation of p53 leads to up-regulation of p21, a CDK5 inhibitor similar to CIP.…”

Section: Discussionmentioning

confidence: 99%

The Cyclin-Dependent Kinase 5 Inhibitor Peptide Inhibits Herpes Simplex Virus Type 1 Replication

Man

Slevin

Petcu

et al. 2019

Sci Rep

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In order to evaluate the influence of CDK5 inhibitory peptide (CIP) on Human alphaherpesvirus 1 (HSV-1) replication, we constructed two recombinant adeno-associated-virus 2 (rAAV2) vectors encoding CIP fused with cyan-fluorescent-protein (CFP), with or without nuclear localization signal. A third vector encoding non-fused CIP and CFP was also constructed. HeLa and HEK 293T cells were infected with the rAAV-CIP vectors at multiplicity of infection (MOI) of 5000, in the absence or presence of a recombinant HSV-1 that encodes a yellow-fluorescent-protein (rHSV48Y; MOI = 1). Cells co-infected with rHSV48Y and rAAV vectors that did not express the CIP gene (rAAV-CFP-Neo) served as controls. At 24 h after infection, the effect of CIP on rHSV48Y replication was assessed by PCR, qRT-PCR, Western-blot, flow-cytometry, epifluorescence and confocal microscopy. We show that in cultures co-infected with rAAV-CFP-Neo, 27% of the CFP-positive cells present rHSV48Y replication compartments. By contrast, in cultures co-infected with CIP-encoding rAAV2 vectors and rHSV48Y only 6–20% of the cells positive for CIP showed rHSV48Y replication compartments, depending on the CIP variant. Flow-cytometry showed that less than 40% of the rHSV48Y/rAAV-CIP, and more than 75% of rHSV48Y/rAAV-CFP-Neo co-infected cells were positive for both transgene products. The microscopy and flow-cytometry data support the hypothesis that CIP is inhibiting HSV-1 replication.

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“…In addition, some viruses specifically interrupt the cellular p53–p21 pathway to modulate the host cell cycle, blocking cellular DNA synthesis in generating viral nucleotide pools, like Respiratory syncytial virus [27], Herpes simplex virus type 2 (HSV-2), and Simian virus 40 (SV40). However, unlike HSV-2, which increases p21 protein levels by phosphorylation of the p53 protein at Ser20 [8], SV40 induced p53 phosphorylation is accompanied by Ser15 [28], as SV40 activating the ATR-Delta p53 signaling to maintain S phase environment, and to manipulate polymerases [17]. This may explain our data that in the CRISPR/Cas 9 mediated 148PK15 P53 − / − cells, PCV2 infection did not induce S phase accumulation, resulting in a relative lower virus production, while the 813PK15 P53m/m cells that mutated original S271 and G272 sites of porcine p53 into R271 showed a slightly weakened function of p53 signaling undergoing PCV2 infection, resulting in a slight relative decreased S phase accumulation compared with the wild-type cell.…”

Section: Discussionmentioning

confidence: 99%

“…Prototype foamy virus (PFV) promotes p53 level increase by knockdown of Pirh2 to contribute to the latency of PFV infection [7]. Herpes simplex virus type 2 infection can phosphorylate p53 protein to induce the G0/G1 phase arrest [8]. PRRSV manipulates the host factors mdm2 and p53 via its Nsp1α to increase viral replication at the early stage of infection [9].…”

Section: Introductionmentioning

confidence: 99%

p53 signaling modulation of cell cycle arrest and viral replication in porcine circovirus type 2 infection cells

Han

et al. 2016

Vet Res

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Porcine circovirus type 2 (PCV2) is a ubiquitous pathogen in the swine industry worldwide. Previous studies have shown that PCV2 infection induces host cell apoptosis through up-regulation of p53. To further identify the regulatory roles of p53 signaling in the process of PCV2 infection, we established p53 gene knockout PK15 cell lines using the genomic editor tool CRISPR/Cas9, and further investigated the roles of p53 in modulating the cell cycle and viral replication in this study. The results show that PCV2 infection induced obvious S phase accumulation in wild-type PK15 cells and a compromised S phase accumulation in the p53 gene mutation cells (813PK15p53m/m), but did not induce obvious S phase accumulation in the p53 gene knockout cells (148PK15p53−/−) compared with the respective mock infection. PCV2 infection activated p53 signaling, up-regulated the expression of p21, Cyclin E, and down-regulated Cyclin A, CDK2. In p53 deficient cells, however, PCV2-induced changes in Cyclin A, CDK2, and Cyclin E were efficiently reversed to the basal levels. Detection of PCV2 replication showed decreased viral ORF1 genomic DNA in p53 deficient cells (148PK15p533−/−) and p53 mutated cells (813PK15p53m/m) compared with p53 wild-type cells after different synchronization treatment. Furthermore, PCV2 viral genomic DNA and Cap protein levels were higher in the cells released from S phase synchronized cells than in the cells released from the G0/G1 phase or G2/M phase-synchronized, or asynchronous cells after 18 h post-infection. Taken together, this study demonstrates that PCV2 infection induces S phase accumulation to favor viral replication in host cells through activation of the p53 pathway.

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Disruption of the p53–p21 pathway inhibits efficiency of the lytic-replication cycle of herpes simplex virus type 2 (HSV-2)

Cited by 4 publications

References 49 publications

Analysis of Virion-Incorporated Host Proteins Required for Herpes Simplex Virus Type 1 Infection through a RNA Interference Screen

Analysis of Virion-Incorporated Host Proteins Required for Herpes Simplex Virus Type 1 Infection through a RNA Interference Screen

The Cyclin-Dependent Kinase 5 Inhibitor Peptide Inhibits Herpes Simplex Virus Type 1 Replication

p53 signaling modulation of cell cycle arrest and viral replication in porcine circovirus type 2 infection cells

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