Hepatitis B virus downregulates the human interferon-inducible MxA promoter through direct interaction of precore/core proteins - PubMed (original) (raw)
. 2003 Aug;84(Pt 8):2073-2082.
doi: 10.1099/vir.0.18966-0.
Affiliations
- PMID: 12867637
- DOI: 10.1099/vir.0.18966-0
Hepatitis B virus downregulates the human interferon-inducible MxA promoter through direct interaction of precore/core proteins
Mario Fernández et al. J Gen Virol. 2003 Aug.
Abstract
The human MxA protein is an interferon (IFN)-inducible GTPase with proven antiviral activity against diverse viruses. IFN responsiveness is impaired in chronic hepatitis B virus (HBV) infection. Accordingly, initial experiments showed that, in contrast to parental HepG2 cells, when HepG2-derived 2.2.15 liver cells carrying the HBV genome were treated with IFN, they could not synthesize the MxA protein. Furthermore, MxA expression was reduced in HepG2 cells transiently transfected with the HBV genome. To assess whether HBV-encoded precore/core (preC/C) proteins interact with the IFN-signalling pathway, HepG2, Chang and HeLa cells were transfected with preC/C expression plasmids; the levels of signal transducers remained unaffected. Next, full-length and deletion mutants fused to the CAT reporter gene were tested to investigate whether MxA inhibition occurs at the promoter level. In co-transfection experiments, IFN-induced CAT activity was inhibited by preC/C expression in a dose-dependent manner. Analysis of deletion mutants showed that the region affected by the preC/C proteins comprises IFN-stimulated response elements 2 and 3, upstream of the putative start codon of the MxA promoter. In addition, HBV preC/C proteins interacted directly with the MxA promoter, as shown by electrophoretic mobility shift assays. These results demonstrate a mechanism that HBV probably uses to downregulate an element of the IFN-induced host antiviral responses, which accounts for the impairment observed in HBV-infected patients.
Similar articles
- Hepatitis C virus core protein down-regulates transcription of interferon-induced antiviral genes.
de Lucas S, Bartolome J, Carreno V. de Lucas S, et al. J Infect Dis. 2005 Jan 1;191(1):93-9. doi: 10.1086/426509. Epub 2004 Nov 29. J Infect Dis. 2005. PMID: 15593009 - [The influence of HBV and its antigens on the expressions of JAK-STAT signal transduction pathway molecules and antiviral proteins of IFN alpha].
Guan SH, Yang K, Lu MJ, Lu YP, Yang DL. Guan SH, et al. Zhonghua Gan Zang Bing Za Zhi. 2011 Jun;19(6):440-4. Zhonghua Gan Zang Bing Za Zhi. 2011. PMID: 22053375 Chinese. - Hepatitis B virus core protein with hot-spot mutations inhibit MxA gene transcription but has no effect on inhibition of virus replication by interferon α.
Zhijian Y, Zhen H, Fan Z, Jin Y, Qiwen D, Zhongming Z. Zhijian Y, et al. Virol J. 2010 Oct 20;7:278. doi: 10.1186/1743-422X-7-278. Virol J. 2010. PMID: 20959021 Free PMC article. - Hepatitis delta virus proteins repress hepatitis B virus enhancers and activate the alpha/beta interferon-inducible MxA gene.
Williams V, Brichler S, Radjef N, Lebon P, Goffard A, Hober D, Fagard R, Kremsdorf D, Dény P, Gordien E. Williams V, et al. J Gen Virol. 2009 Nov;90(Pt 11):2759-2767. doi: 10.1099/vir.0.011239-0. Epub 2009 Jul 22. J Gen Virol. 2009. PMID: 19625466 - The Curious Case of Type I IFN and MxA: Tipping the Immune Balance in AIDS.
Furuya AK, Sharifi HJ, de Noronha CM. Furuya AK, et al. Front Immunol. 2014 Sep 2;5:419. doi: 10.3389/fimmu.2014.00419. eCollection 2014. Front Immunol. 2014. PMID: 25228901 Free PMC article. Review. No abstract available.
Cited by
- Conserved Functions of Orthohepadnavirus X Proteins to Inhibit Type-I Interferon Signaling.
Choonnasard A, Shofa M, Okabayashi T, Saito A. Choonnasard A, et al. Int J Mol Sci. 2024 Mar 28;25(7):3753. doi: 10.3390/ijms25073753. Int J Mol Sci. 2024. PMID: 38612565 Free PMC article. - An HBV susceptibility variant of KNG1 modulates the therapeutic effects of interferons α and λ1 in HBV infection by promoting MAVS lysosomal degradation.
Zhang B, Han H, Zhao X, Li AN, Wang Y, Yuan W, Yang Z, Li MD. Zhang B, et al. EBioMedicine. 2023 Aug;94:104694. doi: 10.1016/j.ebiom.2023.104694. Epub 2023 Jul 11. EBioMedicine. 2023. PMID: 37442062 Free PMC article. - An anti-cancer surveillance by the interplay between interferon-beta and retinoblastoma protein RB1.
Qin A. Qin A. Front Oncol. 2023 Apr 27;13:1173467. doi: 10.3389/fonc.2023.1173467. eCollection 2023. Front Oncol. 2023. PMID: 37182173 Free PMC article. Review. - Immune Checkpoint Inhibitors in HBV-Caused Hepatocellular Carcinoma Therapy.
Zhang J, Hu C, Xie X, Qi L, Li C, Li S. Zhang J, et al. Vaccines (Basel). 2023 Mar 8;11(3):614. doi: 10.3390/vaccines11030614. Vaccines (Basel). 2023. PMID: 36992198 Free PMC article. Review. - Hepatitis B Virus Core Protein Is Not Required for Covalently Closed Circular DNA Transcriptional Regulation.
Zhong Y, Wu C, Xu Z, Teng Y, Zhao L, Zhao K, Wang J, Wang W, Zhan Q, Zhu C, Chen X, Liang K, Cheng X, Xia Y. Zhong Y, et al. J Virol. 2022 Nov 9;96(21):e0136222. doi: 10.1128/jvi.01362-22. Epub 2022 Oct 13. J Virol. 2022. PMID: 36226986 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous