Cooperativity between the 3’ untranslated region microRNA binding sites is critical for the virulence of eastern equine encephalitis virus
Autoři:
Derek W. Trobaugh aff001; Chengqun Sun aff001; Nishank Bhalla aff001; Christina L. Gardner aff001; Matthew Dunn aff001; William B. Klimstra aff001
Působiště autorů:
Center for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America
aff001
Vyšlo v časopise:
Cooperativity between the 3’ untranslated region microRNA binding sites is critical for the virulence of eastern equine encephalitis virus. PLoS Pathog 15(10): e32767. doi:10.1371/journal.ppat.1007867
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.ppat.1007867
Souhrn
Eastern equine encephalitis virus (EEEV), a mosquito-borne RNA virus, is one of the most acutely virulent viruses endemic to the Americas, causing between 30% and 70% mortality in symptomatic human cases. A major factor in the virulence of EEEV is the presence of four binding sites for the hematopoietic cell-specific microRNA, miR-142-3p, in the 3’ untranslated region (3’ UTR) of the virus. Three of the sites are “canonical” with all 7 seed sequence residues complimentary to miR-142-3p while one is “non-canonical” and has a seed sequence mismatch. Interaction of the EEEV genome with miR-142-3p limits virus replication in myeloid cells and suppresses the systemic innate immune response, greatly exacerbating EEEV neurovirulence. The presence of the miRNA binding sequences is also required for efficient EEEV replication in mosquitoes and, therefore, essential for transmission of the virus. In the current studies, we have examined the role of each binding site by point mutagenesis of the seed sequences in all combinations of sites followed by infection of mammalian myeloid cells, mosquito cells and mice. The resulting data indicate that both canonical and non-canonical sites contribute to cell infection and animal virulence, however, surprisingly, all sites are rapidly deleted from EEEV genomes shortly after infection of myeloid cells or mice. Finally, we show that the virulence of a related encephalitis virus, western equine encephalitis virus, is also dependent upon miR-142-3p binding sites.
Klíčová slova:
3' UTR – Bone marrow cells – Cell binding – Microbial mutation – MicroRNAs – Viral replication – Eastern equine encephalitis virus – Western equine encephalitis virus
Zdroje
1. Deresiewicz RL, Thaler SJ, Hsu L, Zamani AA. Clinical and neuroradiographic manifestations of eastern equine encephalitis. N Engl J Med. 1997;336: 1867–1874. doi: 10.1056/NEJM199706263362604 9197215
2. Gardner CL, Burke CW, Tesfay MZ, Glass PJ, Klimstra WB, Ryman KD. Eastern and Venezuelan equine encephalitis viruses differ in their ability to infect dendritic cells and macrophages: impact of altered cell tropism on pathogenesis. J Virol. 2008;82: 10634–10646. doi: 10.1128/JVI.01323-08 18768986
3. Mildner A, Chapnik E, Manor O, Yona S, Kim K-W, Aychek T, et al. Mononuclear phagocyte miRNome analysis identifies miR-142 as critical regulator of murine dendritic cell homeostasis. Blood. 2013;121: 1016–1027. doi: 10.1182/blood-2012-07-445999 23212522
4. Trobaugh DW, Gardner CL, Sun C, Haddow AD, Wang E, Chapnik E, et al. RNA viruses can hijack vertebrate microRNAs to suppress innate immunity. Nature. 2014;506: 245–248. doi: 10.1038/nature12869 24352241
5. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116: 281–297. doi: 10.1016/s0092-8674(04)00045-5 14744438
6. Hutvágner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science. American Association for the Advancement of Science; 2002;297: 2056–2060. doi: 10.1126/science.1073827 12154197
7. Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci USA. 2003;100: 9779–9784. doi: 10.1073/pnas.1630797100 12902540
8. Bartel DP. MicroRNAs: Target Recognition and Regulatory Functions. Cell. 2009;136: 215–233. doi: 10.1016/j.cell.2009.01.002 19167326
9. Agarwal V, Bell GW, Nam J-W, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife. 2015;4: 101. doi: 10.7554/eLife.05005 26267216
10. Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466: 835–840. doi: 10.1038/nature09267 20703300
11. Eichhorn SW, Guo H, McGeary SE, Rodriguez-Mias RA, Shin C, Baek D, et al. mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues. Mol Cell. 2014;56: 104–115. doi: 10.1016/j.molcel.2014.08.028 25263593
12. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science. 2005;309: 1577–1581. doi: 10.1126/science.1113329 16141076
13. Scheel TKH, Luna JM, Liniger M, Nishiuchi E, Rozen-Gagnon K, Shlomai A, et al. A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration. Cell Host Microbe. 2016;19: 409–423. doi: 10.1016/j.chom.2016.02.007 26962949
14. Song L, Liu H, Gao S, Jiang W, Huang W. Cellular microRNAs inhibit replication of the H1N1 influenza A virus in infected cells. J Virol. 2010;84: 8849–8860. doi: 10.1128/JVI.00456-10 20554777
15. Khongnomnan K, Makkoch J, Poomipak W, Poovorawan Y, Payungporn S. Human miR-3145 inhibits influenza A viruses replication by targeting and silencing viral PB1 gene. Exp Biol Med (Maywood). SAGE Publications; 2015;240: 1630–1639. doi: 10.1177/1535370215589051 26080461
16. Ingle H, Kumar S, Raut AA, Mishra A, Kulkarni DD, Kameyama T, et al. The microRNA miR-485 targets host and influenza virus transcripts to regulate antiviral immunity and restrict viral replication. Sci Signal. 2015;8: ra126. doi: 10.1126/scisignal.aab3183 26645583
17. Zheng Z, Ke X, Wang M, He S, Li Q, Zheng C, et al. Human microRNA hsa-miR-296-5p suppresses enterovirus 71 replication by targeting the viral genome. J Virol. 2013;87: 5645–5656. doi: 10.1128/JVI.02655-12 23468506
18. Wen B-P, Dai H-J, Yang Y-H, Zhuang Y, Sheng R. MicroRNA-23b Inhibits Enterovirus 71 Replication through Downregulation of EV71 VPl Protein. Intervirology. 2013;56: 195–200. doi: 10.1159/000348504 23594713
19. Trobaugh DW, Klimstra WB. MicroRNA Regulation of RNA Virus Replication and Pathogenesis. Trends Mol Med. 2017;23: 80–93. doi: 10.1016/j.molmed.2016.11.003 27989642
20. Shimakami T, Yamane D, Jangra RK, Kempf BJ, Spaniel C, Barton DJ, et al. Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proc Natl Acad Sci USA. 2012;109: 941–946. doi: 10.1073/pnas.1112263109 22215596
21. Meister G. Argonaute proteins: functional insights and emerging roles. Nat Rev Genet. Nature Publishing Group; 2013;14: 447–459. doi: 10.1038/nrg3462 23732335
22. Heiss BL, Maximova OA, Thach DC, Speicher JM, Pletnev AG. MicroRNA Targeting of Neurotropic Flavivirus: Effective Control of Virus Escape and Reversion to Neurovirulent Phenotype. J Virol. 2012;86: 5647–5659. doi: 10.1128/JVI.07125-11 22419812
23. Teterina NL, Liu G, Maximova OA, Pletnev AG. Silencing of neurotropic flavivirus replication in the central nervous system by combining multiple microRNA target insertions in two distinct viral genome regions. Virology. 2014;456–457: 247–258. doi: 10.1016/j.virol.2014.04.001 24889244
24. Sun C, Gardner CL, Watson AM, Ryman KD, Klimstra WB. Stable, high-level expression of reporter proteins from improved alphavirus expression vectors to track replication and dissemination during encephalitic and arthritogenic disease. J Virol. 2014;88: 2035–2046. doi: 10.1128/JVI.02990-13 24307590
25. Armstrong PM, Andreadis TG. Eastern Equine Encephalitis Virus in Mosquitoes and Their Role as Bridge Vectors. Emerg Infect Dis. 2010;16: 1869–1874. doi: 10.3201/eid1612.100640 21122215
26. Yao Y, Charlesworth J, Nair V, Watson M. MicroRNA expression profiles in avian haemopoietic cells. Front Genet. 2013;4. doi: 10.3389/fgene.2013.00153 23967013
27. Bingham AM, Burkett-Cadena ND, Hassan HK, McClure CJW, Unnasch TR. Field investigations of winter transmission of eastern equine encephalitis virus in Florida. Am J Trop Med Hyg. 2014;91: 685–693. doi: 10.4269/ajtmh.14-0081 25070997
28. Beug H, Kirchbach von A, Döderlein G, Conscience JF, Graf T. Chicken hematopoietic cells transformed by seven strains of defective avian leukemia viruses display three distinct phenotypes of differentiation. Cell. 1979;18: 375–390. doi: 10.1016/0092-8674(79)90057-6 227607
29. Yao Y, Charlesworth J, Nair V, Watson M. MicroRNA expression profiles in avian haemopoietic cells. Front Genet. Frontiers; 2013;4: 153. doi: 10.3389/fgene.2013.00153 23967013
30. Trobaugh DW, Sun C, Dunn MD, Reed DS, Klimstra WB. Rational design of a live-attenuated eastern equine encephalitis virus vaccine through informed mutation of virulence determinants. PLoS Pathog. 2019;15: e1007584. doi: 10.1371/journal.ppat.1007584 30742691
31. Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011;11: 762–774. doi: 10.1038/nri3070 21984070
32. Jain A, Pasare C. Innate Control of Adaptive Immunity: Beyond the Three-Signal Paradigm. J Immunol. American Association of Immunologists; 2017;198: 3791–3800. doi: 10.4049/jimmunol.1602000 28483987
33. Gardner CL, Ebel GD, Ryman KD, Klimstra WB. Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence. Proc Natl Acad Sci USA. 2011;108: 16026–16031. doi: 10.1073/pnas.1110617108 21896745
34. Gardner CL, Yin J, Burke CW, Klimstra WB, Ryman KD. Type I interferon induction is correlated with attenuation of a South American eastern equine encephalitis virus strain in mice. Virology. Elsevier Inc; 2009;390: 338–347. doi: 10.1016/j.virol.2009.05.030 19539968
35. Hahn CS, Lustig S, Strauss EG, Strauss JH. Western equine encephalitis virus is a recombinant virus. Proc Natl Acad Sci USA. 1988;85: 5997–6001. doi: 10.1073/pnas.85.16.5997 3413072
36. Weaver SC, Kang W, Shirako Y, Rumenapf T, Strauss EG, Strauss JH. Recombinational history and molecular evolution of western equine encephalomyelitis complex alphaviruses. J Virol. American Society for Microbiology (ASM); 1997;71: 613–623. 8985391
37. Levitt NH, Miller HV, Edelman R. Interaction of alphaviruses with human peripheral leukocytes: in vitro replication of Venezuelan equine encephalomyelitis virus in monocyte cultures. Infect Immun. American Society for Microbiology (ASM); 1979;24: 642–646. 468371
38. Pham AM, Langlois RA, tenOever BR. Replication in Cells of Hematopoietic Origin Is Necessary for Dengue Virus Dissemination. Kuhn RJ, editor. PLoS Pathog. 2012;8: e1002465. doi: 10.1371/journal.ppat.1002465 22241991
39. Langlois RA, Varble A, Chua MA, García-Sastre A, tenOever BR. Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune responses. Proc Nat Acad Sci. National Acad Sciences; 2012;109: 12117–12122. doi: 10.1073/pnas.1206039109 22778433
40. Langlois RA, Albrecht RA, Kimble B, Sutton T, Shapiro JS, Finch C, et al. MicrorNA-based strategy to mitigate the risk of gain-of-function influenza studies. Nat Biotechnol. Nature Publishing Group; 2013;31: 844–847. doi: 10.1038/nbt.2666 23934176
41. Hon LS, Zhang Z. The roles of binding site arrangement and combinatorial targeting in microRNA repression of gene expression. Genome Biol. BioMed Central; 2007;8: R166. doi: 10.1186/gb-2007-8-8-r166 17697356
42. Grimson A, Farh KK-H, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell. 2007;27: 91–105. doi: 10.1016/j.molcel.2007.06.017 17612493
43. Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. Combinatorial microRNA target predictions. Nat Genet. 2005;37: 495–500. doi: 10.1038/ng1536 15806104
44. Saetrom P, Heale BSE, Snøve O, Aagaard L, Alluin J, Rossi JJ. Distance constraints between microRNA target sites dictate efficacy and cooperativity. Nucleic Acids Res. 2007;35: 2333–2342. doi: 10.1093/nar/gkm133 17389647
45. Lecellier C-H, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, et al. A cellular microRNA mediates antiviral defense in human cells. Science. 2005;308: 557–560. doi: 10.1126/science.1108784 15845854
46. Bai XT, Nicot C. miR-28-3p Is a Cellular Restriction Factor That Inhibits Human T Cell Leukemia Virus, Type 1 (HTLV-1) Replication and Virus Infection. J Biol Chem. 2015;290: 5381–5390. doi: 10.1074/jbc.M114.626325 25568327
47. Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19: 92–105. doi: 10.1101/gr.082701.108 18955434
48. Luna JM, Scheel TKH, Danino T, Shaw KS, Mele A, Fak JJ, et al. Hepatitis C Virus RNA Functionally Sequesters miR-122. Cell. 2015;160: 1099–1110. doi: 10.1016/j.cell.2015.02.025 25768906
49. Hyde JL, Chen R, Trobaugh DW, Diamond MS, Weaver SC, Klimstra WB, et al. The 5”and 3” ends of alphavirus RNAs—Non-coding is not non-functional. Virus Res. 2015;206: 99–107. doi: 10.1016/j.virusres.2015.01.016 25630058
50. Aguilar PV, Adams AP, Wang E, Kang W, Carrara A-S, Anishchenko M, et al. Structural and nonstructural protein genome regions of eastern equine encephalitis virus are determinants of interferon sensitivity and murine virulence. J Virol. 2008;82: 4920–4930. doi: 10.1128/JVI.02514-07 18353963
51. Logue CH, Bosio CF, Welte T, Keene KM, Ledermann JP, Phillips A, et al. Virulence variation among isolates of western equine encephalitis virus in an outbred mouse model. J Gen Virol. 2009;90: 1848–1858. doi: 10.1099/vir.0.008656-0 19403754
52. Bhalla N, Sun C, Metthew Lam LK, Gardner CL, Ryman KD, Klimstra WB. Host translation shutoff mediated by non-structural protein 2 is a critical factor in the antiviral state resistance of Venezuelan equine encephalitis virus. Virology. 2016;496: 147–165. doi: 10.1016/j.virol.2016.06.005 27318152
53. Watson AM, Lam LKM, Klimstra WB, Ryman KD. The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells. Pierson TC, editor. PLoS Pathog. 2016;12: e1005786–29. doi: 10.1371/journal.ppat.1005786 27463517
54. Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS. MicroRNA targets in Drosophila. Genome Biol. 2003;5: R1. doi: 10.1186/gb-2003-5-1-r1 14709173
55. John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human MicroRNA targets. James Carrington C, editor. Plos Biol. Public Library of Science; 2004;2: e363. doi: 10.1371/journal.pbio.0020363 15502875
Štítky
Hygiena a epidemiologie Infekční lékařství LaboratořČlánek vyšel v časopise
PLOS Pathogens
2019 Číslo 10
- Perorální antivirotika jako vysoce efektivní nástroj prevence hospitalizací kvůli COVID-19 − otázky a odpovědi pro praxi
- Stillova choroba: vzácné a závažné systémové onemocnění
- Diagnostický algoritmus při podezření na syndrom periodické horečky
- Jak souvisí postcovidový syndrom s poškozením mozku?
- Choroby jater v ordinaci praktického lékaře – význam jaterních testů
Nejčtenější v tomto čísle
- Alterations in cellular expression in EBV infected epithelial cell lines and tumors
- Correction: A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes
- Influenza virus polymerase subunits co-evolve to ensure proper levels of dimerization of the heterotrimer
- Induction of PGRN by influenza virus inhibits the antiviral immune responses through downregulation of type I interferons signaling