Human Interferon Regulatory Factor 2 Gene Expression is Induced in Chronic Hepatitis C Virus Infection—A Possible Mode of Viral Persistence

Mukherjee, Rathindra Mohan; Bansode, Budhapriyavilas; Gangwal, Puja; Jakkampudi, Aparna; Reddy, P. Balkumar; Rao, Padaki Nagaraja; Gupta, Rajesh; Reddy, D. Nageshwar

doi:10.1016/s0973-6883(12)60080-2

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…IRF2 suppresses the activity of IRF1 by competing for binding sites ( 28 ). An increase in the IRF1/IRF2 ratio has been considered an important event needed for the transcriptional activation of IFNα genes required for the development of cellular responses to viruses ( 29 ). Limited and not very well-replicated studies have reported an association of IRF2 polymorphism with susceptibility to the autoimmune disease systemic lupus erythematosus (SLE).…”

Section: Implications For Irfs In Disease Pathogenesis–why Target Thementioning

confidence: 99%

Therapeutic Targeting of IRFs: Pathway-Dependence or Structure-Based?

2018

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The interferon regulatory factors (IRFs) are a family of master transcription factors that regulate pathogen-induced innate and acquired immune responses. Aberration(s) in IRF signaling pathways due to infection, genetic predisposition and/or mutation, which can lead to increased expression of type I interferon (IFN) genes, IFN-stimulated genes (ISGs), and other pro-inflammatory cytokines/chemokines, has been linked to the development of numerous diseases, including (but not limited to) autoimmune and cancer. What is currently lacking in the field is an understanding of how best to therapeutically target these transcription factors. Many IRFs are regulated by post-translational modifications downstream of pattern recognition receptors (PRRs) and some of these modifications lead to activation or inhibition. We and others have been able to utilize structural features of the IRFs in order to generate dominant negative mutants that inhibit function. Here, we will review potential therapeutic strategies for targeting all IRFs by using IRF5 as a candidate targeting molecule.

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Section: Implications For Irfs In Disease Pathogenesis–why Target Thementioning

confidence: 99%

Therapeutic Targeting of IRFs: Pathway-Dependence or Structure-Based?

2018

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“…Upon capturing the gel image by Bio-Capt imazer (Vilber Lourmat, France), the integrated density of DNA band was evaluated by using the software Image J 1.42 (Broken Symmetry Software, USA) in respect to the known standard marker as a control with units nanogram per milliliters (ng/ml) and further normalized against the housekeeping gene beta actin used as internal control to define the expression of respective genes by the density of the band. 26 Polymerase…”

Section: Polymerase Chain Reaction Amplification Of High Mobility Gromentioning

confidence: 99%

Reduced Expression of DNA Damage Repair Genes High Mobility Group Box1 and Poly(ADP-ribose) Polymerase1 in Inactive Carriers of Hepatitis B Virus Infection-A Possible Stage of Viral Integration

Mukherjee

Shravanti

Jakkampudi

et al. 2013

Journal of Clinical and Experimental Hepatology

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Background: High mobility group box1 (HMGB1) and poly(ADP-ribose) polymerase1 (PARP1) proteins repair cellular DNA damage. Reduced expression of the corresponding genes can lead to an impaired DNA damage repair mechanism. Intracellular replication of hepatitis B virus (HBV) in such conditions can favor the integration of viral DNA into host genome leading to the development of hepatocellular carcinoma (HCC). Objective: This study was performed to assess the expression of HMGB1 and PARP1 mRNAs in conjunction with the estimation of HBV replication intermediate pregenomic RNA (PgRNA) in various phases of HBV infection. Materials: Eighty eight patients and 26 voluntary blood donors as controls were included in the study. Patients were grouped in to acute (AHB; n = 15), inactive carriers (IC; n = 36), cirrhosis (Cirr; n = 25) and hepatocellular carcinoma (HCC; n = 12). Serum HBV DNA was quantified by real time polymerase chain reaction (PCR) assay. Expression of HMGB1, PARP1 and PgRNA were evaluated using peripheral blood mononuclear cells (PBMCs) derived RNA by reverse transcription PCR (RT-PCR) and densitometry. Results: Significant reduction of HMGB1 and PARP1 gene expressions (P < 0.05) were observed in patients than controls with more explicit decline of PARP1 (P = 0.0002). Both genes were significantly downregulated (P < 0.001) in ICs than controls. In ICs, HMGB1 was significantly lowered than cirrhosis (P = 0.002) and HCC (P = 0.0006) while PARP1 declined significantly (P = 0.04) than HCC. Level of PgRNA was comparable in all the disease categories. Conclusion: In conclusion, our findings indicate impaired DNA damage repair mechanisms in HBV infected cells of ICs. This, along with low viral load but higher level of PgRNA in this group is suggestive of the diversion of HBV replication pathway that might facilitate viral DNA integration in to host genome. Intrusion of HBV PgRNA reverse transcription in early stage of infection might appear advantageous to thwart the development of HCC. ( J CLIN EXP HEPATOL 2013;3:89-95)

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“…However, this anti-viral immunity must be balanced by a complicated network (pathways) in cells. As two antagonism transcription regulators, IRF1 and IRF2 play important roles in type I interferon-induced antiviral effect [ 29 – 31 ]. As previously reported, IRF1 could be induced by many cytokines such as IFNs (-α, -β, -γ), TNF-α, IL-1, IL-6, LIF and virus infection mediated by STAT and NF-κB [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

IRF2 inhibits ZIKV replication by promoting FAM111A expression to enhance the host restriction effect of RFC3

Ren

Zhu

Sun

et al. 2021

Virol J

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Background Although interferon regulatory factor 2 (IRF2) was reported to stimulate virus replication by suppressing the type I interferon signaling pathway, because cell cycle arrest was found to promote viral replication, IRF2-regulated replication fork factor (FAM111A and RFC3) might be able to affect ZIKV replication. In this study, we aimed to investigate the function of IRF2, FAM111A and RFC3 to ZIKV replication and underlying mechanism. Methods siIRF2, siFAM111A, siRFC3 and pIRF2 in ZIKV-infected A549, 2FTGH and U5A cells were used to explore the mechanism of IRF2 to inhibit ZIKV replication. In addition, their expression was analyzed by RT-qPCR and western blots, respectively. Results In this study, we found IRF2 expression was increased in ZIKV-infected A549 cells and IRF2 inhibited ZIKV replication independent of type I IFN signaling pathway. IRF2 could activate FAM111A expression and then enhanced the host restriction effect of RFC3 to inhibit replication of ZIKV. Conclusions We speculated the type I interferon signaling pathway might not play a leading role in regulating ZIKV replication in IRF2-silenced cells. We found IRF2 was able to upregulate FAM111A expression and thus enhance the host restriction effect of RFC3 on ZIKV.

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Human Interferon Regulatory Factor 2 Gene Expression is Induced in Chronic Hepatitis C Virus Infection—A Possible Mode of Viral Persistence

Cited by 6 publications

References 35 publications

Therapeutic Targeting of IRFs: Pathway-Dependence or Structure-Based?

Therapeutic Targeting of IRFs: Pathway-Dependence or Structure-Based?

Reduced Expression of DNA Damage Repair Genes High Mobility Group Box1 and Poly(ADP-ribose) Polymerase1 in Inactive Carriers of Hepatitis B Virus Infection-A Possible Stage of Viral Integration

IRF2 inhibits ZIKV replication by promoting FAM111A expression to enhance the host restriction effect of RFC3

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