1887

Abstract

Hepatitis E virus (HEV) induces interferons and regulates the induction of interferon-stimulated genes (ISGs) in the host cell. HEV infection has been shown to promote the expression of different ISGs, such as ISG15, IFIT1, MX1, RSAD2/Viperin and CxCL10, in cell culture and animal models. Interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) is an ISG-encoded protein that inhibits the translation of viral RNA, having 5′-triphosphate or the mRNA lacking 2′-O-methylation on the 5′cap. In this study, we found that IFIT1 binds to HEV RNA to inhibit its translation. HEV replication is also restricted in hepatoma cells with overexpressed IFIT1. However, despite this binding of IFIT1 to HEV RNA, HEV successfully replicates in hepatoma cells in the infection scenario. In an effort to identify the underlying mechanism, we found that HEV RNA-dependent RNA polymerase (RdRp) binds to IFIT1, thereby protecting the viral RNA from IFIT1-mediated translation inhibition. RdRp sequesters IFIT1, resulting in the successful progression of viral replication in the infected cells. Thus, we discovered a distinct pro-viral role of HEV RdRp that is crucial for successful infection in the host, and propose a unique mechanism developed by HEV to overcome IFIT1-mediated host immune response.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001229
2019-01-31
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/100/3/471.html?itemId=/content/journal/jgv/10.1099/jgv.0.001229&mimeType=html&fmt=ahah

References

  1. Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA et al. Virus Taxonomy VIIIth Report of the ICTV London, UK: Elsevie, Academic Press; 2005 pp. 851–855
    [Google Scholar]
  2. Cao D, Meng XJ. Molecular biology and replication of hepatitis E virus. Emerg Microbes Infect 2012; 1:e17 [View Article]
    [Google Scholar]
  3. van der Poel WHM, Dalton HR, Johne R, Pavio N, Bouwknegt M et al. Knowledge gaps and research priorities in the prevention and control of hepatitis E virus infection. Transbound Emerg Dis 2018; 65:22–29 [View Article][PubMed]
    [Google Scholar]
  4. Vasickova P, Psikal I, Kralik P, Widen F, Hubalek Z et al. Hepatitis E virus: a review. Veterinární Medicína 2008; 52:365–384 [View Article]
    [Google Scholar]
  5. Meng XJ. Hepatitis E virus: animal reservoirs and zoonotic risk. Vet Microbiol 2010; 140:256–265 [View Article][PubMed]
    [Google Scholar]
  6. Helsen N, Debing Y, Paeshuyse J, Dallmeier K, Boon R et al. Stem cell-derived hepatocytes: A novel model for hepatitis E virus replication. J Hepatol 2016; 64:565–573 [View Article][PubMed]
    [Google Scholar]
  7. Wu X, Dao Thi VL, Liu P, Takacs CN, Xiang K et al. Pan-Genotype Hepatitis E Virus Replication in Stem Cell–Derived Hepatocellular Systems. Gastroenterology 154:663–674
    [Google Scholar]
  8. Allweiss L, Gass S, Giersch K, Groth A, Kah J et al. Human liver chimeric mice as a new model of chronic hepatitis E virus infection and preclinical drug evaluation. J Hepatol 2016; 64:1033–1040 [View Article][PubMed]
    [Google Scholar]
  9. Sayed IM, Foquet L, Verhoye L, Abravanel F, Farhoudi A et al. Transmission of hepatitis E virus infection to human-liver chimeric FRG mice using patient plasma. Antiviral Res 2017; 141:150–154 [View Article][PubMed]
    [Google Scholar]
  10. van de Garde MD, Pas SD, van der Net G, de Man RA, Osterhaus AD et al. Hepatitis E virus (HEV) genotype 3 infection of human liver chimeric mice as a model for chronic HEV infection. J Virol 2016; 90:4394–4401 [View Article][PubMed]
    [Google Scholar]
  11. van de Garde MDB, Pas SD, van Oord GW, Gama L, Choi Y et al. Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice. Sci Rep 2017; 7:8267 [View Article][PubMed]
    [Google Scholar]
  12. Nan Y, Yu Y, Ma Z, Khattar SK, Fredericksen B et al. Hepatitis E Virus Inhibits Type I Interferon Induction by ORF1 Product. J Virol 2014; 88:8696–8705
    [Google Scholar]
  13. Nan Y, Ma Z, Wang R, Yu Y, Kannan H et al. Enhancement of interferon induction by ORF3 product of hepatitis E virus. J Virol 2014; 88:8696–8705 [View Article][PubMed]
    [Google Scholar]
  14. Yin X, Li X, Ambardekar C, Hu Z, Lhomme S et al. Hepatitis E virus persists in the presence of a type III interferon response. PLoS Pathog 2017; 13:e1006417 [View Article][PubMed]
    [Google Scholar]
  15. Devhare PB, Desai S, Lole KS. Innate immune responses in human hepatocyte-derived cell lines alter genotype 1 hepatitis E virus replication efficiencies. Sci Rep 2016; 6:26827 [View Article][PubMed]
    [Google Scholar]
  16. Sooryanarain H, Rogers AJ, Cao D, Haac MER, Karpe YA et al. ISG15 modulates type I interferon signaling and the antiviral response during Hepatitis E virus replication. J Virol 2017; 91:e0062117 [View Article][PubMed]
    [Google Scholar]
  17. Fensterl V, Sen GC. Interferon-induced Ifit proteins: their role in viral pathogenesis. J Virol 2015; 89:2462–2468 [View Article][PubMed]
    [Google Scholar]
  18. Andrejeva J, Norsted H, Habjan M, Thiel V, Goodbourn S et al. ISG56/IFIT1 is primarily responsible for interferon-induced changes to patterns of parainfluenza virus type 5 transcription and protein synthesis. J Gen Virol 2013; 94:59–68 [View Article]
    [Google Scholar]
  19. Kumar P, Sweeney TR, Skabkin MA, Skabkina OV, Hellen CU et al. Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5'-terminal regions of cap0-, cap1- and 5'ppp- mRNAs. Nucleic Acids Res 2014; 42:3228–3245 [View Article][PubMed]
    [Google Scholar]
  20. Daffis S, Szretter KJ, Schriewer J, Li J, Youn S et al. 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature 2010; 468:452–456 [View Article][PubMed]
    [Google Scholar]
  21. Hyde JL, Diamond MS. Innate immune restriction and antagonism of viral RNA lacking 2′-O methylation. Virology 2015; 479-480:66–74 [View Article][PubMed]
    [Google Scholar]
  22. Hui DJ, Bhasker CR, Merrick WC, Sen GC. Viral stress-inducible protein p56 inhibits translation by blocking the interaction of eIF3 with the ternary complex eIF2.GTP.Met-tRNAi. J Biol Chem 2003; 278:39477–39482 [View Article][PubMed]
    [Google Scholar]
  23. Hui DJ, Terenzi F, Merrick WC, Sen GC. Mouse p56 blocks a distinct function of eukaryotic initiation factor 3 in translation initiation. J Biol Chem 2005; 280:3433–3440 [View Article][PubMed]
    [Google Scholar]
  24. Young DF, Andrejeva J, Li X, Inesta-Vaquera F, Dong C et al. Human IFIT1 Inhibits mRNA Translation of Rubulaviruses but Not Other Members of the Paramyxoviridae Family. J Virol 2016; 90:9446–9456 [View Article][PubMed]
    [Google Scholar]
  25. Fraser CS, Doudna JA. Structural and mechanistic insights into hepatitis C viral translation initiation. Nat Rev Microbiol 2007; 5:29–38 [View Article][PubMed]
    [Google Scholar]
  26. Wang C, Pflugheber J, Sumpter R, Sodora DL, Hui D et al. Alpha interferon induces distinct translational control programs to suppress hepatitis C virus RNA replication. J Virol 2003; 77:3898–3912 [View Article][PubMed]
    [Google Scholar]
  27. Lopez-Rodriguez R, Trapero-Marugan M, Borque MJ, Roman M, Hernandez-Bartolome A et al. Genetic variants of interferon-stimulated genes and IL-28B as host prognostic factors of response to combination treatment for chronic hepatitis C. Clin Pharmacol Ther 2011; 90:712–721 [View Article][PubMed]
    [Google Scholar]
  28. Terenzi F, Saikia P, Sen GC. Interferon-inducible protein, P56, inhibits HPV DNA replication by binding to the viral protein E1. EMBO J 2008; 27:3311–3321 [View Article][PubMed]
    [Google Scholar]
  29. Ojha NK, Lole KS. Hepatitis E virus ORF1 encoded non structural protein-host protein interaction network. Virus Res 2016; 213:195–204 [View Article][PubMed]
    [Google Scholar]
  30. Nair VP, Anang S, Subramani C, Madhvi A, Bakshi K et al. Endoplasmic reticulum stress induced synthesis of a novel viral factor mediates efficient replication of genotype-1 hepatitis E virus. PLoS Pathog 2016; 12:e1005521 [View Article][PubMed]
    [Google Scholar]
  31. Reynaud JM, Kim DY, Atasheva S, Rasalouskaya A, White JP et al. IFIT1 differentially interferes with translation and replication of alphavirus genomes and promotes induction of type I interferon. PLoS Pathog 2015; 11:e1004863 [View Article][PubMed]
    [Google Scholar]
  32. Hyde JL, Gardner CL, Kimura T, White JP, Liu G et al. A viral RNA structural element alters host recognition of nonself RNA. Science 2014; 343:783–787 [View Article][PubMed]
    [Google Scholar]
  33. Kimura T, Katoh H, Kayama H, Saiga H, Okuyama M et al. Ifit1 inhibits Japanese encephalitis virus replication through binding to 5' capped 2'-O unmethylated RNA. J Virol 2013; 87:9997–10003 [View Article][PubMed]
    [Google Scholar]
  34. Cho H, Shrestha B, Sen GC, Diamond MS. A role for Ifit2 in restricting West Nile virus infection in the brain. J Virol 2013; 87:8363–8371 [View Article][PubMed]
    [Google Scholar]
  35. Habjan M, Hubel P, Lacerda L, Benda C, Holze C et al. Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA. PLoS Pathog 2013; 9:e1003663 [View Article][PubMed]
    [Google Scholar]
  36. Züst R, Cervantes-Barragan L, Habjan M, Maier R, Neuman BW et al. Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat Immunol 2011; 12:137–143 [View Article][PubMed]
    [Google Scholar]
  37. Menachery VD, Yount BL, Josset L, Gralinski LE, Scobey T et al. Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 2'-o-methyltransferase activity. J Virol 2014; 88:4251–4264 [View Article][PubMed]
    [Google Scholar]
  38. Fensterl V, Wetzel JL, Ramachandran S, Ogino T, Stohlman SA et al. Interferon-induced Ifit2/ISG54 protects mice from lethal VSV neuropathogenesis. PLoS Pathog 2012; 8:e1002712 [View Article][PubMed]
    [Google Scholar]
  39. Reguera J, Weber F, Cusack S. Bunyaviridae RNA polymerases (L-protein) have an N-terminal, influenza-like endonuclease domain, essential for viral cap-dependent transcription. PLoS Pathog 2010; 6:e1001101 [View Article][PubMed]
    [Google Scholar]
  40. Rahmeh AA, Schenk AD, Danek EI, Kranzusch PJ, Liang B et al. Molecular architecture of the vesicular stomatitis virus RNA polymerase. Proc Natl Acad Sci USA 2010; 107:20075–20080 [View Article][PubMed]
    [Google Scholar]
  41. Egloff MP, Benarroch D, Selisko B, Romette JL, Canard B. An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization. EMBO J 2002; 21:2757–2768 [View Article][PubMed]
    [Google Scholar]
  42. Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S et al. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA 2009; 15:2340–2350 [View Article][PubMed]
    [Google Scholar]
  43. Yu GY, He G, Li CY, Tang M, Grivennikov S et al. Hepatic expression of HCV RNA-dependent RNA polymerase triggers innate immune signaling and cytokine production. Mol Cell 2012; 48:313–321 [View Article][PubMed]
    [Google Scholar]
  44. Painter MM, Morrison JH, Zoecklein LJ, Rinkoski TA, Watzlawik JO et al. Antiviral protection via RdRP-mediated stable activation of innate immunity. PLoS Pathog 2015; 11:e1005311 [View Article][PubMed]
    [Google Scholar]
  45. Delgui LR, Colombo MI. A novel mechanism underlying the innate immune response induction upon viral-dependent replication of host cell mrna: a mistake of +sRNA viruses' replicases. Front Cell Infect Microbiol 2017; 7:5 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001229
Loading
/content/journal/jgv/10.1099/jgv.0.001229
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error