Differences in processing determinants of nonstructural polyprotein and in the Sequence of nonstructural protein 3 affect neurovirulence of Semliki Forest virus

Journal of Virology

Volumn 89, Issue 21, 2015, Pages 11030-11045

  Saul, Sirle ^a   Ferguson, Mhairi ^b,c   Cordonin, Colette ^d   Fragkoudis, Rennos ^b,c   Ool, Margit ^a   Tamberg, Nele ^a   Sherwood, Karen ^c,e   Fazakerley, John K ^b,c   Merits, Andres ^a  

^a UNIVERSITY OF TARTU   (Estonia)

^b INSTITUTE FOR ANIMAL HEALTH   (United Kingdom)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

^d UNIVERSITÉ DE LA RÉUNION   (France)

^e Peace Arch Hospital   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; GLUTAMIC ACID; HISTIDINE; NONSTRUCTURAL PROTEIN 1; NONSTRUCTURAL PROTEIN 2; NONSTRUCTURAL PROTEIN 3; NONSTRUCTURAL PROTEIN 4; POLYPROTEIN; VALINE; COMPLEMENTARY DNA; NSP3 PROTEIN, SEMLIKI FOREST VIRUS; RECOMBINANT PROTEIN; RNA BINDING PROTEIN; VIRAL PROTEIN;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; GENE INSERTION; GENE SEQUENCE; MOLECULAR CLONING; MOUSE; NONHUMAN; NSP3 GENE; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN PROCESSING; PROTEIN STABILITY; SEMLIKI FOREST VIRUS; VIRUS RECOMBINANT; VIRUS VIRULENCE; ANIMAL; BIOSYNTHESIS; CELL LINE; FLUORESCENCE MICROSCOPY; GENETICS; IMMUNOBLOTTING; METABOLISM; NERVE CELL; NONPARAMETRIC TEST; PATHOGENICITY; PHYSIOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; VIROLOGY; VIRULENCE;

AMINO ACID SUBSTITUTION; ANIMALS; CELL LINE; DNA, COMPLEMENTARY; IMMUNOBLOTTING; MICE; MICROSCOPY, FLUORESCENCE; NEURONS; PROTEIN PROCESSING, POST-TRANSLATIONAL; RECOMBINANT PROTEINS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA-BINDING PROTEINS; SEMLIKI FOREST VIRUS; STATISTICS, NONPARAMETRIC; VIRAL NONSTRUCTURAL PROTEINS; VIRULENCE;

EID: 84945205368     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01186-15     Document Type: Article

References (58)

1. Allsopp TE, Fazakerley JK. 2000. Altruistic cell suicide and the specialized case of the virus-infected nervous system. Trends Neurosci 23:284-290. http://dx.doi.org/10.1016/S0166-2236(00)01591-5.
2. Fazakerley JK, Cotterill CL, Lee G, Graham A. 2006. Virus tropism, distribution, persistence and pathology in the corpus callosum of the Semliki Forest virus-infected mouse brain: a novel system to study virusoligodendrocyte interactions. Neuropathol Appl Neurobiol 32:397-409. http://dx.doi.org/10.1111/j.1365-2990.2006.00739.x.
3. Gates MC, Sheahan BJ, O'Sullivan MA, Atkins GJ. 1985. The pathogenicity of the A7, M9 and L10 strains of Semliki Forest virus for weanling mice and primary mouse brain cell cultures. J Gen Virol 66:2365-2373. http://dx.doi.org/10.1099/0022-1317-66-11-2365.
4. Fazakerley JK, Pathak S, Scallan M, Amor S, Dyson H. 1993. Replication of the A7(74) strain of Semliki Forest virus is restricted in neurons. Virology 195:627-637. http://dx.doi.org/10.1006/viro.1993.1414.
5. Fragkoudis R, Tamberg N, Siu R, Kiiver K, Kohl A, Merits A, Fazakerley JK. 2009. Neurons and oligodendrocytes in the mouse brain differ in their ability to replicate Semliki Forest virus. J Neurovirol 15:57-70. http://dx.doi.org/10.1080/13550280802482583.
6. Strauss JH, Strauss EG. 1994. The alphaviruses: gene expression, replication, and evolution. Microbiol Rev 58:491-562.
7. Fazakerley JK. 2002. Pathogenesis of Semliki Forest virus encephalitis. J Neurovirol 8(Suppl 2):S66-S74.
8. Varjak M, Saul S, Arike L, Lulla A, Peil L, Merits A. 2013. Magnetic fractionation and proteomic dissection of cellular organelles occupied by the late replication complexes of Semliki Forest virus. J Virol 87:10295-10312. http://dx.doi.org/10.1128/JVI.01105-13.
9. Shirako Y, Strauss JH. 1994. Regulation of Sindbis virus RNA replication: uncleaved P123 and nsP4 function in minus-strand RNA synthesis, whereas cleaved products from P123 are required for efficient plus-strand RNA synthesis. J Virol 68:1874-1885.
10. Salonen A, Vasiljeva L, Merits A, Magden J, Jokitalo E, Kaariainen L. 2003. Properly folded nonstructural polyprotein directs the Semliki Forest virus replication complex to the endosomal compartment. J Virol 77: 1691-1702. http://dx.doi.org/10.1128/JVI.77.3.1691-1702.2003.
11. Ahola T, Lampio A, Auvinen P, Kaariainen L. 1999. Semliki Forest virus mRNA capping enzyme requires association with anionic membrane phospholipids for activity. EMBO J 18:3164-3172. http://dx.doi.org/10.1093/emboj/18.11.3164.
12. Lulla V, Sawicki DL, Sawicki SG, Lulla A, Merits A, Ahola T. 2008. Molecular defects caused by temperature-sensitive mutations in Semliki Forest virus nsP1. J Virol 82:9236-9244. http://dx.doi.org/10.1128/JVI.00711-08.
13. Cruz CC, Suthar MS, Montgomery SA, Shabman R, Simmons J, Johnston RE, Morrison TE, Heise MT. 2010. Modulation of type I IFN induction by a virulence determinant within the alphavirus nsP1 protein. Virology 399:1-10. http://dx.doi.org/10.1016/j.virol.2009.12.031.
14. Deuber SA, Pavlovic J. 2007. Virulence of a mouse-adapted Semliki Forest virus strain is associated with reduced susceptibility to interferon. J Gen Virol 88:1952-1959. http://dx.doi.org/10.1099/vir.0.82264-0.
15. Rikkonen M, Peranen J, Kaariainen L. 1994. ATPase and GTPase activities associated with Semliki Forest virus nonstructural protein nsP2. J Virol 68:5804-5810.
16. Vasiljeva L, Merits A, Auvinen P, Kaariainen L. 2000. Identification of a novel function of the Alphavirus capping apparatus RNA 5=- triphosphatase activity of Nsp2. J Biol Chem 275:17281-17287. http://dx.doi.org/10.1074/jbc.M910340199.
17. Das PK, Merits A, Lulla A. 2014. Functional cross-talk between distant domains of Chikungunya virus non-structural protein 2 is decisive for its RNA-modulating activity. J Biol Chem 289:5635-5653. http://dx.doi.org/10.1074/jbc.M113.503433.
18. Lulla A, Lulla V, Merits A. 2012. Macromolecular assembly-driven processing of the 2/3 cleavage site in the alphavirus replicase polyprotein. J Virol 86:553-565. http://dx.doi.org/10.1128/JVI.05195-11.
19. Fazakerley JK, Boyd A, Mikkola ML, Kaariainen L. 2002. A single amino acid change in the nuclear localization sequence of the nsP2 protein affects the neurovirulence of Semliki Forest virus. J Virol 76:392-396. http://dx.doi.org/10.1128/JVI.76.1.392-396.2002.
20. Merits A, Vasiljeva L, Ahola T, Kaariainen L, Auvinen P. 2001. Proteolytic processing of Semliki Forest virus-specific non-structural polyprotein by nsP2 protease. J Gen Virol 82:765-773. http://dx.doi.org/10.1099/0022-1317-82-4-765.
21. Tamm K, Merits A, Sarand I. 2008. Mutations in the nuclear localization signal of nsP2 influencing RNA synthesis, protein expression and cytotoxicity of Semliki Forest virus. J Gen Virol 89:676-686. http://dx.doi.org/10.1099/vir.0.83320-0.
22. Shin G, Yost SA, Miller MT, Elrod EJ, Grakoui A, Marcotrigiano J. 2012. Structural and functional insights into alphavirus polyprotein processing and pathogenesis. Proc Natl Acad Sci U S A 109:16534-16539. http://dx.doi.org/10.1073/pnas.1210418109.
23. Neuvonen M, Kazlauskas A, Martikainen M, Hinkkanen A, Ahola T, Saksela K. 2011. SH3 domain-mediated recruitment of host cell amphiphysins by alphavirus nsP3 promotes viral RNA replication. PLoS Pathog 7:e1002383. http://dx.doi.org/10.1371/journal.ppat.1002383.
24. Vihinen H, Ahola T, Tuittila M, Merits A, Kaariainen L. 2001. Elimination of phosphorylation sites of Semliki Forest virus replicase protein nsP3. J Biol Chem 276:5745-5752. http://dx.doi.org/10.1074/jbc.M006077200.
25. Rubach JK, Wasik BR, Rupp JC, Kuhn RJ, Hardy RW, Smith JL. 2009. Characterization of purified Sindbis virus nsP4 RNA-dependent RNA polymerase activity in vitro. Virology 384:201-208. http://dx.doi.org/10.1016/j.virol.2008.10.030.
26. de Groot RJ, Rumenapf T, Kuhn RJ, Strauss EG, Strauss JH. 1991. Sindbis virus RNApolymerase is degraded by the N-end rule pathway. Proc Natl Acad SciUS A88:8967-8971. http://dx.doi.org/10.1073/pnas.88.20.8967.
27. McIntosh BM, Worth CB, Kokernot RH. 1961. Isolation of Semliki Forest virus from Aedes (Aedimorphus) argenteopunctatus (Theobald) collected in Portuguese East Africa. Trans R Soc Trop Med Hyg 55:192-198. http://dx.doi.org/10.1016/0035-9203(61)90025-6.
28. Amor S, Scallan MF, Morris MM, Dyson H, Fazakerley JK. 1996. Role of immune responses in protection and pathogenesis during Semliki Forest virus encephalitis. J Gen Virol 77:281-291. http://dx.doi.org/10.1099/0022-1317-77-2-281.
29. Atkins GJ. 1983. The avirulent A7 strain of Semliki Forest virus has reduced cytopathogenicity for neuroblastoma cells compared to the virulent L10 strain. J Gen Virol 64:1401-1404. http://dx.doi.org/10.1099/0022-1317-64-6-1401.
30. Bradish CJ, Allner K, Maber HB. 1971. The virulence of original and derived strains of Semliki Forest virus for mice, guinea-pigs and rabbits. J Gen Virol 12:141-160. http://dx.doi.org/10.1099/0022-1317-12-2-141.
31. Atkins GJ, Sheahan BJ, Liljestrom P. 1999. The molecular pathogenesis of Semliki Forest virus: a model virus made useful? J Gen Virol 80:2287-2297. http://dx.doi.org/10.1099/0022-1317-80-9-2287.
32. Tuittila M, Hinkkanen AE. 2003. Amino acid mutations in the replicase protein nsP3 of Semliki Forest virus cumulatively affect neurovirulence. J Gen Virol 84:1525-1533. http://dx.doi.org/10.1099/vir.0.18936-0.
33. Tuittila MT, Santagati MG, Roytta M, Maatta JA, Hinkkanen AE. 2000. Replicase complex genes of Semliki Forest virus confer lethal neurovirulence. J Virol 74:4579-4589. http://dx.doi.org/10.1128/JVI.74.10.4579-4589.2000.
34. Ferguson MC, Saul S, Fragkoudis R, Weisheit S, Cox J, Patabendige A, Sherwood K, Watson M, Merits A, Fazakerley JK. 2015. Ability of the encephalitic arbovirus Semliki Forest virus to cross the blood-brain barrier is determined by the charge of the E2 glycoprotein. J Virol 89:7536-7549. http://dx.doi.org/10.1128/JVI.03645-14.
35. Ulper L, Sarand I, Rausalu K, Merits A. 2008. Construction, properties, and potential application of infectious plasmids containing Semliki Forest virus full-length cDNA with an inserted intron. J Virol Methods 148:265-270. http://dx.doi.org/10.1016/j.jviromet.2007.10.007.
36. Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ. 2009. Jalview version 2: a multiple sequence alignment editor and analysis workbench. Bioinformatics 25:1189-1191. http://dx.doi.org/10.1093/bioinformatics/btp033.
37. Gorchakov R, Frolova E, Williams BR, Rice CM, Frolov I. 2004. PKR-dependent and-independent mechanisms are involved in translational shutoff during Sindbis virus infection. J Virol 78:8455-8467. http://dx.doi.org/10.1128/JVI.78.16.8455-8467.2004.
38. Lulla A, Lulla V, Tints K, Ahola T, Merits A. 2006. Molecular determinants of substrate specificity for Semliki Forest virus nonstructural protease. J Virol 80:5413-5422. http://dx.doi.org/10.1128/JVI.00229-06.
39. Lulla V, Karo-Astover L, Rausalu K, Merits A, Lulla A. 2013. Presentation overrides specificity: probing the plasticity of alphaviral proteolytic activity through mutational analysis. J Virol 87:10207-10220. http://dx.doi.org/10.1128/JVI.01485-13.
40. Zusinaite E, Tints K, Kiiver K, Spuul P, Karo-Astover L, Merits A, Sarand I. 2007. Mutations at the palmitoylation site of non-structural protein nsP1 of Semliki Forest virus attenuate virus replication and cause accumulation of compensatory mutations. J Gen Virol 88:1977-1985. http://dx.doi.org/10.1099/vir.0.82865-0.
41. Tamberg N, Lulla V, Fragkoudis R, Lulla A, Fazakerley JK, Merits A. 2007. Insertion of EGFP into the replicase gene of Semliki Forest virus results in a novel, genetically stable marker virus. J Gen Virol 88:1225-1230. http://dx.doi.org/10.1099/vir.0.82436-0.
42. Peranen J, Laakkonen P, Hyvonen M, Kaariainen L. 1995. The alphavirus replicase protein nsP1 is membrane-associated and has affinity to endocytic organelles. Virology 208:610-620. http://dx.doi.org/10.1006/viro.1995.1192.
43. Peranen J, Rikkonen M, Liljestrom P, Kaariainen L. 1990. Nuclear localization of Semliki Forest virus-specific nonstructural protein nsP2. J Virol 64:1888-1896.
44. Panas MD, Varjak M, Lulla A, Eng KE, Merits A, Karlsson Hedestam GB, McInerney GM. 2012. Sequestration of G3BP coupled with efficient translation inhibits stress granules in Semliki Forest virus infection. Mol Biol Cell 23:4701-4712. http://dx.doi.org/10.1091/mbc.E12-08-0619.
45. Gorchakov R, Garmashova N, Frolova E, Frolov I. 2008. Different types of nsP3-containing protein complexes in Sindbis virus-infected cells. J Virol 82:10088-10101. http://dx.doi.org/10.1128/JVI.01011-08.
46. de Groot RJ, Hardy WR, Shirako Y, Strauss JH. 1990. Cleavage-site preferences of Sindbis virus polyproteins containing the non-structural proteinase. Evidence for temporal regulation of polyprotein processing in vivo. EMBO J 9:2631-2638.
47. Russo AT, Malmstrom RD, White MA, Watowich SJ. 2010. Structural basis for substrate specificity of alphavirus nsP2 proteases. J Mol Graph Model 29:46-53. http://dx.doi.org/10.1016/j.jmgm.2010.04.005.
48. Lemm JA, Rice CM. 1993. Roles of nonstructural polyproteins and cleavage products in regulating Sindbis virus RNA replication and transcription. J Virol 67:1916-1926.
49. Heise MT, White LJ, Simpson DA, Leonard C, Bernard KA, Meeker RB, Johnston RE. 2003. An attenuating mutation in nsP1 of the Sindbis-group virus S.A.AR86 accelerates nonstructural protein processing and upregulates viral 26S RNA synthesis. J Virol 77:1149-1156. http://dx.doi.org/10.1128/JVI.77.2.1149-1156.2003.
50. Park E, Griffin DE. 2009. The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice. Virology 388:305-314. http://dx.doi.org/10.1016/j.virol.2009.03.031.
51. Akhrymuk I, Kulemzin SV, Frolova EI. 2012. Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II. J Virol 86:7180-7191. http://dx.doi.org/10.1128/JVI.00541-12.
52. Garmashova N, Gorchakov R, Frolova E, Frolov I. 2006. Sindbis virus nonstructural protein nsP2 is cytotoxic and inhibits cellular transcription. J Virol 80:5686-5696. http://dx.doi.org/10.1128/JVI.02739-05.
53. Simmons JD, Wollish AC, Heise MT. 2010. A determinant of Sindbis virus neurovirulence enables efficient disruption of Jak/STAT signaling. J Virol 84:11429-11439. http://dx.doi.org/10.1128/JVI.00577-10.
54. Myles KM, Kelly CL, Ledermann JP, Powers AM. 2006. Effects of an opal termination codon preceding the nsP4 gene sequence in the O'Nyong- Nyong virus genome on Anopheles gambiae infectivity. J Virol 80:4992-4997. http://dx.doi.org/10.1128/JVI.80.10.4992-4997.2006.
55. Egloff MP, Malet H, Putics A, Heinonen M, Dutartre H, Frangeul A, Gruez A, Campanacci V, Cambillau C, Ziebuhr J, Ahola T, Canard B. 2006. Structural and functional basis for ADP-ribose and poly(ADPribose) binding by viral macro domains. J Virol 80:8493-8502. http://dx.doi.org/10.1128/JVI.00713-06.
56. Malet H, Coutard B, Jamal S, Dutartre H, Papageorgiou N, Neuvonen M, Ahola T, Forrester N, Gould EA, Lafitte D, Ferron F, Lescar J, Gorbalenya AE, de Lamballerie X, Canard B. 2009. The crystal structures of Chikungunya and Venezuelan equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket. J Virol 83:6534-6545. http://dx.doi.org/10.1128/JVI.00189-09.
57. Park E, Griffin DE. 2009. Interaction of Sindbis virus non-structural protein 3 with poly(ADP-ribose) polymerase1in neuronal cells. JGenVirol 90:2073-2080. http://dx.doi.org/10.1099/vir.0.012682-0.
58. Panas MD, Ahola T, McInerney GM. 2014. The C-terminal repeat domains of nsP3 from the Old World alphaviruses bind directly to G3BP. J Virol 88:5888-5893. http://dx.doi.org/10.1128/JVI.00439-14.