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Hepatitis

Host-cell interactions in HBV infection and pathogenesis: the emerging role of m6A modification

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Pages 2264-2275 | Received 30 Aug 2021, Accepted 10 Nov 2021, Published online: 01 Dec 2021

References

  • Glebe D, Bremer CM. The molecular virology of hepatitis B virus. Semin Liver Dis. 2013;33(2):103–112.
  • Desrosiers R, Friderici K, Rottman F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc Natl Acad Sci. 1974;71(10):3971–3975.
  • Myhrvold C, Freije CA, Gootenberg JS, et al. Field-deployable viral diagnostics using CRISPR-Cas13. Science. 2018 Apr;360(6387):444–448.
  • Liu J, Yue Y, Han D, et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol. 2014 Feb;10(2):93–95.
  • Meyer KD, Jaffrey SR. The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat Rev Mol Cell Biol. 2014;15(5):313–326.
  • Zheng G, Dahl JA, Niu Y, et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2013 Jan;49(1):18–29.
  • Gulati P, Avezov E, Ma M, et al. Fat mass and obesity-related (FTO) shuttles between the nucleus and cytoplasm. Biosci Rep. 2014;34(5):e00144.
  • Xu C, Wang X, Liu K, et al. Structural basis for selective binding of m 6 A RNA by the YTHDC1 YTH domain. Nat Chem Biol. 2014;10(11):927–929.
  • Wang X, Zhao BS, Roundtree IA, et al. N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell. 2015 Jun;161(6):1388–1399.
  • Xiao W, Adhikari S, Dahal U, et al. Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Mol Cell. 2016 Feb;61(4):507–519.
  • Wu B, Su S, Patil DP, et al. Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1. Nat Commun. 2018;9(1):1–12.
  • Manners O, Baquero-Perez B, Whitehouse A. M6a: widespread regulatory control in virus replication. Biochim Biophys Acta (BBA)-Gene Regul Mech. 2019;1862(3):370–381.
  • Imam H, Khan M, Gokhale NS, et al. N6-methyladenosine modification of hepatitis B virus RNA differentially regulates the viral life cycle. Proc Natl Acad Sci U S A. 2018 Aug;115(35):8829–8834.
  • Fleming AM, Nguyen NLB, Burrows CJ. Colocalization of m(6)A and G-quadruplex-forming sequences in viral RNA (HIV, zika, hepatitis B, and SV40) suggests topological control of adenosine N (6)-methylation. ACS Cent Sci. 2019 Feb;5(2):218–228.
  • Mo J, Chen Z, Qin S, et al. TRADES: targeted RNA demethylation by SunTag system. Adv Sci (Weinheim, Baden-Wurttemberg, Ger). 2020 Aug;7(19):2001402.
  • Ko C, Chakraborty A, Chou W-M, et al. Hepatitis B virus (HBV) genome recycling and de novo secondary infection events maintain stable cccDNA levels. J Hepatol. 2018;69(6):1231–1241.
  • Murphy CM, Xu Y, Li F, et al. Hepatitis B virus X protein promotes degradation of SMC5/6 to enhance HBV replication. Cell Rep. 2016;16(11):2846–2854.
  • Kim G-W, Siddiqui A. Hepatitis B virus X protein recruits methyltransferases to affect cotranscriptional N6-methyladenosine modification of viral/host RNAs. Proc Natl Acad Sci U S A. 2021 Jan;118(3):e2019455118.
  • Kim G-W, Imam H, Siddiqui A. The RNA binding proteins YTHDC1 and FMRP regulate the nuclear export of N6-methyladenosine modified hepatitis B virus transcripts and affect the viral life cycle. J Virol. 2021 Apr;95(13):e0009721.
  • Winkler R, Gillis E, Lasman L, et al. m 6 A modification controls the innate immune response to infection by targeting type I interferons. Nat Immunol. 2019;20(2):173–182.
  • Yoneyama M, Kikuchi M, Natsukawa T, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol. 2004 Jul;5(7):730–737.
  • Zheng Q, Hou J, Zhou Y, et al. The RNA helicase DDX46 inhibits innate immunity by entrapping m6A-demethylated antiviral transcripts in the nucleus. Nat Immunol. 2017;18(10):1094–1103.
  • Zhang Y, Wang X, Zhang X, et al. RNA-binding protein YTHDF3 suppresses interferon-dependent antiviral responses by promoting FOXO3 translation. Proc Natl Acad Sci U S A. 2019 Jan;116(3):976–981.
  • Wang L, Wen M, Cao X. Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses. Science. 2019 Aug;365(6454):eaav0758.
  • Schlee M, Hartmann G. Discriminating self from non-self in nucleic acid sensing. Nat Rev Immunol. 2016;16(9):566–580.
  • Karikó K, Buckstein M, Ni H, et al. Suppression of RNA recognition by toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity. 2005;23(2):165–175.
  • Durbin AF, Wang C, Marcotrigiano J, et al. RNAs containing modified nucleotides fail to trigger RIG-I conformational changes for innate immune signaling. MBio. 2016;7(5):e00833–16.
  • Kim G-W, Imam H, Khan M, et al. N (6)-methyladenosine modification of hepatitis B and C viral RNAs attenuates host innate immunity via RIG-I signaling. J Biol Chem. 2020 Sep;295(37):13123–13133.
  • Chen S, Kumar S, Espada CE, et al. N 6-methyladenosine modification of HIV-1 RNA suppresses type-I interferon induction in differentiated monocytic cells and primary macrophages. PLoS Pathog. 2021;17(3):e1009421.
  • Lu M, Zhang Z, Xue M, et al. N 6-methyladenosine modification enables viral RNA to escape recognition by RNA sensor RIG-I. Nat Microbiol. 2020;5(4):584–598.
  • Qiu W, Zhang Q, Zhang R, et al. N6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA. Nat Commun. 2021;12(1):1582.
  • Liu J, Xu Y-P, Li K, et al. The m(6)A methylome of SARS-CoV-2 in host cells. Cell Res. 2021 Jan;31:404–414.
  • Sato S, Li K, Kameyama T, et al. The RNA Sensor RIG-I dually functions as an innate sensor and direct antiviral factor for Hepatitis B virus. Immunity. 2015;42(1):123–132.
  • Lu H-L, Liao F. Melanoma differentiation–associated gene 5 senses hepatitis B virus and activates innate immune signaling to suppress virus replication. J Immunol. 2013;191(6):3264–3276.
  • Lauterbach-Rivière L, Bergez M, Mönch S, et al. Hepatitis B virus DNA is a substrate for the cGAS/STING pathway but is not sensed in infected hepatocytes. Viruses. 2020;12(6):592.
  • Mutz P, Metz P, Lempp FA, et al. HBV bypasses the innate immune response and does not protect HCV from antiviral activity of interferon. Gastroenterology. 2018;154(6):1791–1804.
  • Yu S, Chen J, Wu M, et al. Hepatitis B virus polymerase inhibits RIG-I-and toll-like receptor 3-mediated beta interferon induction in human hepatocytes through interference with interferon regulatory factor 3 activation and dampening of the interaction between TBK1/IKKε and DDX3. J Gen Virol. 2010;91(8):2080–2090.
  • Wieland SF, Chisari F V. Stealth and cunning: hepatitis B and hepatitis C viruses. J Virol. 2005 Aug;79(15):9369–9380.
  • Suslov A, Boldanova T, Wang X, et al. Hepatitis B virus does not interfere with innate immune responses in the human liver. Gastroenterology. 2018;154(6):1778–1790.
  • Visvanathan K, Skinner NA, Thompson AJ V, et al. Regulation of toll-like receptor-2 expression in chronic hepatitis B by the precore protein. Hepatology. 2007;45(1):102–110.
  • Lang T, Lo C, Skinner N, et al. The hepatitis B e antigen (HBeAg) targets and suppresses activation of the toll-like receptor signaling pathway. J Hepatol. 2011 Oct;55(4):762–769.
  • Wei C, Ni C, Song T, et al. The hepatitis B virus X protein disrupts innate immunity by downregulating mitochondrial antiviral signaling protein. J Immunol. 2010 Jul;185(2):1158–1168.
  • Zoulim F, Durantel D. Antiviral therapies and prospects for a cure of chronic hepatitis B. Cold Spring Harb Perspect Med [Internet]. 2015 Apr 1;5(4):a021501. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25833942.
  • Imam H, Kim G-W, Mir SA, et al. Interferon-stimulated gene 20 (ISG20) selectively degrades N6-methyladenosine modified hepatitis B virus transcripts. PLoS Pathog. 2020 Feb;16(2):e1008338.
  • Li S, Zhu M, Pan R, et al. The tumor suppressor PTEN has a critical role in antiviral innate immunity. Nat Immunol. 2016;17(3):241–249.
  • Kim G-W, Imam H, Khan M, et al. HBV-Induced increased N6 Methyladenosine modification of PTEN RNA affects innate immunity and contributes to HCC. Hepatology. 2021 Feb;73(2):533–547.
  • Kietzmann T. Metabolic zonation of the liver: the oxygen gradient revisited. Redox Biol. 2017;11:622–630.
  • Wing PAC, Liu PJ, Harris JM, et al. Hypoxia inducible factors regulate hepatitis B virus replication by activating the basal core promoter. J Hepatol. 2021;75(1):64–73.
  • Yang N, Wang T, Li Q, et al. HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of HIF-1α. J Cell Physiol. 2021 May;236(5):3863–3880.
  • Wang Y-J, Yang B, Lai Q, et al. Reprogramming of m(6)A epitranscriptome is crucial for shaping of transcriptome and proteome in response to hypoxia. RNA Biol. 2021 Jan;18(1):131–143.
  • Zhong L, Liao D, Zhang M, et al. YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma. Cancer Lett. 2019 Feb;442:252–261.
  • Li Q, Ni Y, Zhang L, et al. HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation. Signal Transduct Target Ther. 2021;6(1):76.
  • Ozakyol A. Global epidemiology of hepatocellular carcinoma (HCC epidemiology). J Gastrointest Cancer. 2017;48(3):238–240.
  • Levrero M, Zucman-Rossi J. Mechanisms of HBV-induced hepatocellular carcinoma. J Hepatol. 2016;64(1):S84–101.
  • Pan X-Y, Huang C, Li J. The emerging roles of m(6)A modification in liver carcinogenesis. Int J Biol Sci. 2021 Jan;17(1):271–284.
  • Rao X, Lai L, Li X, et al. N6-methyladenosine modification of circular RNA circ-ARL3 facilitates hepatitis B virus-associated hepatocellular carcinoma via sponging miR-1305. IUBMB Life. 2021;73(2):408–417.
  • Patop IL, Wüst S, Kadener S. Past, present, and future of circ RNA s. EMBO J. 2019;38(16):e100836.
  • Tang J, Wan Q, Lu J. The prognostic values of m6A RNA methylation regulators in uveal melanoma. BMC Cancer. 2020;20(1):674.
  • Huarte M. The emerging role of lncRNAs in cancer. Nat Med. 2015;21(11):1253–1261.
  • Zhu S, Ye H, Xu X, et al. Involvement of TRPC7-AS1 expression in hepatitis B virus-related hepatocellular carcinoma. J Oncol. 2021;13(13):3115.
  • Alfano V, Zeisel MB, Levrero M, et al. The lncRNAs in HBV-related HCCs: Targeting chromatin Dynamics and beyond. Cancers (Basel). 2021;13(13):3115.
  • Carnero A, Paramio JM. The PTEN/PI3 K/AKT pathway in vivo, cancer mouse models. Front Oncol. 2014;4(252).
  • Fang Q, Chen H. The significance of m6A RNA methylation regulators in predicting the prognosis and clinical course of HBV-related hepatocellular carcinoma. Mol Med. 2020 Jun;26(1):60.
  • Ding W, Wang M, Yu J, et al. HBV/pregenomic RNA increases the stemness and promotes the development of HBV-Related HCC through reciprocal regulation With insulin-like growth factor 2 mRNA-binding protein 3. Hepatology. 2021;74(3):1480–1495.
  • Lichinchi G, Gao S, Saletore Y, et al. Dynamics of the human and viral m(6)A RNA methylomes during HIV-1 infection of T cells. Nat Microbiol. 2016 Feb;1:16011.
  • Gokhale NS, McIntyre ABR, McFadden MJ, et al. N6-Methyladenosine in flaviviridae viral RNA genomes regulates infection. Cell Host Microbe. 2016 Nov;20(5):654–665.
  • Hesser CR, Karijolich J, Dominissini D, et al. N6-methyladenosine modification and the YTHDF2 reader protein play cell type specific roles in lytic viral gene expression during Kaposi’s sarcoma-associated herpesvirus infection. PLoS Pathog. 2018 Apr;14(4):e1006995.
  • Lang F, Singh RK, Pei Y, et al. EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis. PLoS Pathog. 2019 Jun;15(6):e1007796.
  • Tsai K, Courtney DG, Cullen BR. Addition of m6A to SV40 late mRNAs enhances viral structural gene expression and replication. PLoS Pathog. 2018;14(2):e1006919.
  • Dominissini D, Moshitch-Moshkovitz S, Schwartz S, et al. Topology of the human and mouse m 6 A RNA methylomes revealed by m 6 A-seq. Nature. 2012;485(7397):201–206.
  • Adhikari S, Xiao W, Zhao Y-L. m(6)A: signaling for mRNA splicing. RNA Biol [Internet]. 2016 Sep;13(9):756–759. Available from: https://pubmed.ncbi.nlm.nih.gov/27351695.
  • Price AM, Hayer KE, McIntyre ABR, et al. Direct RNA sequencing reveals m6A modifications on adenovirus RNA are necessary for efficient splicing. Nat Commun. 2020;11(1):6016.
  • Ye F, Chen ER, Nilsen TW. Kaposi’s Sarcoma-Associated herpesvirus utilizes and manipulates RNA N(6)-adenosine methylation To promote lytic replication. J Virol. 2017 Aug;91(16):e00466–17.
  • Chulanov VP, Shipulin GA, Schaefer S, et al. Kinetics of HBV DNA and HBsAg in acute hepatitis B patients with and without coinfection by other hepatitis viruses. J Med Virol. 2003 Mar;69(3):313–323.
  • Tu T, Budzinska MA, Shackel NA, et al. HBV DNA integration: molecular mechanisms and Clinical Implications. Protzer U, nassal M, editors. Viruses [Internet]. 2017 Apr 10;9(4):75. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408681/.
  • Tavis JE, Ganem D. Evidence for activation of the hepatitis B virus polymerase by binding of its RNA template. J Virol. 1996;70(9):5741–5750.
  • Wang J, Shen T, Huang X, et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. J Hepatol. 2016;65(4):700–710.
  • Shen S, Xie Z, Cai D, et al. Biogenesis and molecular characteristics of serum hepatitis B virus RNA. PLoS Pathog. 2020;16(10):e1008945.
  • Kostyusheva A, Kostyushev D, Brezgin S, et al. Clinical implications of hepatitis B virus RNA and covalently closed circular DNA in monitoring patients with chronic hepatitis B today with a gaze into the future: the field is unprepared for a sterilizing cure. Genes (Basel). 2018;9(10):483.
  • Capitanchik C, Toolan-Kerr P, Luscombe NM, et al. How do you identify m6 a methylation in transcriptomes at high resolution? a comparison of recent datasets. Front Genet. 2020;11:398.