Arsenicals, the Integrated Stress Response, and Epstein–Barr Virus Lytic Gene Expression

Lee, Jaeyeun; Stone, Jennifer; Desai, Prashant; Kosowicz, John G.; Liu, Jun O.; Ambinder, Richard F.

doi:10.3390/v13050812

Cited by 6 publications

(7 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that nel navir can decrease overall translation rates and facilitate transcriptional activity characteristic of the ISR [20]. We have also shown this recently with the antimicrobial drug, clofoctol and arsenic, in EBV positive cell lines [30,31]. This may be one of the mechanisms by which nel navir inhibits virus capsid maturation: by altering the expression of an essential structural protein.…”

Section: Kshv Virus Protein Expression In Nel Navir Treated Cellssupporting

confidence: 53%

“…Three PCR Master Mixes were created to detect DNA sequences associated with the GAPDH, CHOP, and Trib3 genes. Each of the master mixes contained the Bio-Rad SsoFast EvaGreen supermix, RNase/DNase-free water, and forward and reverse primers [30,31] Immunoblots 5r219 cells (1 × 10 6 ) were harvested 72 h post-induction. Cell pellets were lysed in 2X Laemmli buffer and 10% of this sample was resolved using NuPAGE 4-12% Bis-Tris gels (Thermo Fisher) and transferred to nitrocellulose membranes using the iBlot2 system (Thermo Fisher), as described by Luitweiler et al [32].…”

Section: Rt Qpcrmentioning

confidence: 99%

See 1 more Smart Citation

Nelfinavir Inhibition of Kaposi’s sarcoma-associated herpesvirus protein expression and capsid assembly

Li,

Smith,

Lee

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Antiviral therapies that target herpesviruses are clinically important. Nelfinavir is a protease inhibitor that targets the human immunodeficiency virus (HIV) infections aspartyl protease. Previous studies demonstrated that this drug could also inhibit Kaposi’s sarcoma-associated herpesvirus (KSHV) production. Our laboratory demonstrated nelfinavir can effectively inhibit herpes simplex virus type 1 (HSV-1) replication. For HSV-1 we were able to determine that virus capsids were assembled and exited the nucleus but did not mature in the cytoplasm indicating the drug inhibited secondary envelopment of virions. Methods For KSHV, we recently derived a tractable cell culture system that allowed us to analyze the virus replication cycle in detail. We used this system to further define the stage at which nelfinavir inhibits KSHV replication. Results We discovered that nelfinavir inhibits KSHV extracellular virus production. This was seen when the drug was incubated with the cells for 3 days and when we pulsed the cells with the drug for 1–5 minutes. When KSHV infected cells exposed to the drug were examined using ultrastructural methods there was an absence of mature capsids in the nucleus indicating a defect in capsid assembly. Because nelfinavir influences the integrated stress response (ISR), we examined the expression of viral proteins in the presence of the drug. We observed that the expression of many were significantly changed in the presence of drug. The accumulation of the capsid triplex protein ORF26 was markedly reduced. This is an essential protein required for herpesvirus capsid assembly. Conclusions Our studies confirm that nelfinavir inhibits KSHV virion production by disrupting virus assembly and maturation. Of interest is that inhibition requires only a short exposure to drug. The source of infectious virus in saliva has not been defined in detail but may well be lymphocytes or other cells in the oral mucosa. Thus, it might be that a “swish and spit” exposure rather than systemic administration would prevent virion production.

show abstract

Section: Kshv Virus Protein Expression In Nel Navir Treated Cellssupporting

confidence: 53%

Section: Rt Qpcrmentioning

confidence: 99%

Nelfinavir Inhibition of Kaposi’s sarcoma-associated herpesvirus protein expression and capsid assembly

Li,

Smith,

Lee

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Even at a low concentration, PM2.5 was significantly correlated with the incidence of SQC and AdC [202]. Importantly, arsenic trioxide (As2O3) is another environmental contaminant (present in water, air, and food) related to LC that can activate EBV lytic gene expression in epithelial cells [203]. However, As2O3 is also able to decrease cell proliferation, promote apoptosis, and exhibit anti-angiogenesis properties in the lungs, inhibiting tumor metastasis [204].…”

Section: Ebv Interactions With Other Environmental Contaminants In Lu...mentioning

confidence: 99%

Epstein–Barr Virus Infection in Lung Cancer: Insights and Perspectives

et al. 2022

View full text Add to dashboard Cite

Lung cancer (LC) is the leading cause of cancer death worldwide. Tobacco smoke is the most frequent risk factor etiologically associated with LC, although exposures to other environmental factors such as arsenic, radon or asbestos are also involved. Additionally, the involvement of some viral infections such as high-risk human papillomaviruses (HR-HPVs), Merkel cell polyomavirus (MCPyV), Jaagsiekte Sheep Retrovirus (JSRV), John Cunningham Virus (JCV), and Epstein–Barr virus (EBV) has been suggested in LC, though an etiological relationship has not yet been established. EBV is a ubiquitous gamma herpesvirus causing persistent infections and some lymphoid and epithelial tumors. Since EBV is heterogeneously detected in LCs from different parts of the world, in this review we address the epidemiological and experimental evidence of a potential role of EBV. Considering this evidence, we propose mechanisms potentially involved in EBV-associated lung carcinogenesis. Additional studies are warranted to dissect the role of EBV in this very frequent malignancy.

show abstract

“…Unlike As 2 O 3 , BTdCPU induced RNA expression of gp110 and gp350. Treatment with both drugs reversed this effect [ 166 ].…”

Section: Factors Involved In Ebv Reactivationmentioning

confidence: 99%

Stress-Induced Epstein-Barr Virus Reactivation

Sausen

Bhutta

Gallo³

et al. 2021

Biomolecules

View full text Add to dashboard Cite

Epstein-Barr virus (EBV) is typically found in a latent, asymptomatic state in immunocompetent individuals. Perturbations of the host immune system can stimulate viral reactivation. Furthermore, there are a myriad of EBV-associated illnesses including various cancers, post-transplant lymphoproliferative disease, and autoimmune conditions. A thorough understanding of this virus, and the interplay between stress and the immune system, is essential to establish effective treatment. This review will provide a summary of the interaction between both psychological and cellular stressors resulting in EBV reactivation. It will examine mechanisms by which EBV establishes and maintains latency and will conclude with a brief overview of treatments targeting EBV.

show abstract

Arsenicals, the Integrated Stress Response, and Epstein–Barr Virus Lytic Gene Expression

Cited by 6 publications

References 32 publications

Nelfinavir Inhibition of Kaposi’s sarcoma-associated herpesvirus protein expression and capsid assembly

Nelfinavir Inhibition of Kaposi’s sarcoma-associated herpesvirus protein expression and capsid assembly

Epstein–Barr Virus Infection in Lung Cancer: Insights and Perspectives

Stress-Induced Epstein-Barr Virus Reactivation

Contact Info

Product

Resources

About