An A14U substitution in the 3' noncoding region of the M segment of viral RNA supports replication of influenza virus with an NS1 deletion by modulating alternative splicing of M segment mRNAs

Journal of Virology

Volumn 89, Issue 20, 2015, Pages 10273-10285

  Zheng, Min ^a,b   Wang, Pui ^a,b   Song, Wenjun ^a,b   Lau, Siu Ying ^a   Liu, Siwen ^a   Huang, Xiaofeng ^a   Mok, Bobo Wing Yee ^a   Liu, Yen Chin ^a   Chen, Yixin ^c   Yuen, Kwok Yung ^a,b   Chen, Honglin ^a,b  

^a THE UNIVERSITY OF HONG KONG   (Hong Kong)

^b UNIVERSITY OF HONG KONG   (Hong Kong)

^c XIAMEN UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; INTERFERON; MESSENGER RNA; NONSTRUCTURAL PROTEIN 1; PROTEIN M; PROTEIN M2; SELENOCYSTEINE; UNCLASSIFIED DRUG; VIRUS PROTEIN; VIRUS RNA; 3' UNTRANSLATED REGION; INS1 PROTEIN, INFLUENZA VIRUS; RNA SPLICING;

3' UNTRANSLATED REGION; ALTERNATIVE RNA SPLICING; AMINO ACID SUBSTITUTION; ARTICLE; CONTROLLED STUDY; DOWN REGULATION; EMBRYO; HUMAN; HUMAN CELL; INFLUENZA; INFLUENZA VIRUS; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; RNA SYNTHESIS; RNA TRANSCRIPTION; SEQUENCE ANALYSIS; VIRUS GENOME; VIRUS REPLICATION; ANIMAL; CHLOROCEBUS AETHIOPS; DEFICIENCY; DOG; GENE DELETION; GENETICS; HEK293 CELL LINE; INFLUENZA A VIRUS; MDCK CELL LINE; METABOLISM; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; POINT MUTATION; RNA SPLICING; VERO CELL LINE;

3' UNTRANSLATED REGIONS; ALTERNATIVE SPLICING; ANIMALS; BASE SEQUENCE; CERCOPITHECUS AETHIOPS; DOGS; GENOME, VIRAL; HEK293 CELLS; HUMANS; INFLUENZA A VIRUS; MADIN DARBY CANINE KIDNEY CELLS; MOLECULAR SEQUENCE DATA; POINT MUTATION; RNA SPLICE SITES; RNA, VIRAL; SEQUENCE DELETION; VERO CELLS; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

EID: 84942133730     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.00919-15     Document Type: Article

References (51)

1. Taubenberger JK, Kash JC. 2010. Influenza virus evolution, host adaptation, and pandemic formation. Cell Host Microbe 7:440-451. http://dx.doi.org/10.1016/j.chom.2010.05.009.
2. Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. 1992. Evolution and ecology of influenza A viruses. Microbiol Rev 56:152-179.
3. Palese P, Shaw ML. 2006. Orthmyxoviridae: the viruses and their replication, p 1647-1689. In Knipe DM, Howley P (ed), Fields virology, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA.
4. Nelson MI, Viboud C, Simonsen L, Bennett RT, Griesemer SB, St George K, Taylor J, Spiro DJ, Sengamalay NA, Ghedin E, Taubenberger JK, Holmes EC. 2008. Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918. PLoS Pathog 4:e1000012. http://dx.doi.org/10.1371/journal.ppat.1000012.
5. Naffakh N, Tomoiu A, Rameix-Welti MA, van der Werf S. 2008. Host restriction of avian influenza viruses at the level of the ribonucleoproteins. Annu Rev Microbiol 62:403-424. http://dx.doi.org/10.1146/annurev.micro.62.081307.162746.
6. Eisfeld AJ, Neumann G, Kawaoka Y. 2015. At the centre: influenza A virus ribonucleoproteins. Nat Rev Microbiol 13:28-41. http://dx.doi.org/10.1038/nrmicro3367.
7. Wise HM, Hutchinson EC, Jagger BW, Stuart AD, Kang ZH, Robb N, Schwartzman LM, Kash JC, Fodor E, Firth AE, Gog JR, Taubenberger JK, Digard P. 2012. Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain. PLoS Pathog 8:e1002998. http://dx.doi.org/10.1371/journal.ppat.1002998.
8. Wise HM, Foeglein A, Sun J, Dalton RM, Patel S, Howard W, Anderson EC, Barclay WS, Digard P. 2009. A complicated message: identification of a novel PB1-related protein translated from influenza A virus segment 2 mRNA. J Virol 83:8021-8031. http://dx.doi.org/10.1128/JVI.00826-09.
9. Jagger BW, Wise HM, Kash JC, Walters KA, Wills NM, Xiao YL, Dunfee RL, Schwartzman LM, Ozinsky A, Bell GL, Dalton RM, Lo A, Efstathiou S, Atkins JF, Firth AE, Taubenberger JK, Digard P. 2012. An overlapping protein-coding region in influenza A virus segment 3 modulates the host response. Science 337:199-204. http://dx.doi.org/10.1126/science.1222213.
10. Chen W, Calvo PA, Malide D, Gibbs J, Schubert U, Bacik I, Basta S, O'Neill R, Schickli J, Palese P, Henklein P, Bennink JR, Yewdell JW. 2001. A novel influenza A virus mitochondrial protein that induces cell death. Nat Med 7:1306-1312. http://dx.doi.org/10.1038/nm1201-1306.
11. Wise HM, Barbezange C, Jagger BW, Dalton RM, Gog JR, Curran MD, Taubenberger JK, Anderson EC, Digard P. 2011. Overlapping signals for translational regulation and packaging of influenza A virus segment 2. Nucleic Acids Res 39:7775-7790. http://dx.doi.org/10.1093/nar/gkr487.
12. Shi M, Jagger BW, Wise HM, Digard P, Holmes EC, Taubenberger JK. 2012. Evolutionary conservation of the PA-X open reading frame in segment 3 of influenza A virus. J Virol 86:12411-12413. http://dx.doi.org/10.1128/JVI.01677-12.
13. Brooke CB, Ince WL, Wrammert J, Ahmed R, Wilson PC, Bennink JR, Yewdell JW. 2013. Most influenza a virions fail to express at least one essential viral protein. J Virol 87:3155-3162. http://dx.doi.org/10.1128/JVI.02284-12.
14. Rossman JS, Jing X, Leser GP, Lamb RA. 2010. Influenza virus M2 protein mediates ESCRT-independent membrane scission. Cell 142:902-913. http://dx.doi.org/10.1016/j.cell.2010.08.029.
15. Pinto LH, Dieckmann GR, Gandhi CS, Papworth CG, Braman J, Shaughnessy MA, Lear JD, Lamb RA, DeGrado WF. 1997. A functionally defined model for theM2proton channel of influenza A virus suggests a mechanism for its ion selectivity. Proc Natl Acad Sci U S A 94:11301-11306. http://dx.doi.org/10.1073/pnas.94.21.11301.
16. Cao S, Liu X, Yu M, Li J, Jia X, Bi Y, Sun L, Gao GF, Liu W. 2012. A nuclear export signal in the matrix protein of influenza A virus is required for efficient virus replication. J Virol 86:4883-4891. http://dx.doi.org/10.1128/JVI.06586-11.
17. Valcarcel J, Portela A, Ortin J. 1991. Regulated M1 mRNA splicing in influenza virus-infected cells. J Gen Virol 72:1301-1308. http://dx.doi.org/10.1099/0022-1317-72-6-1301.
18. Chua MA, Schmid S, Perez JT, Langlois RA, Tenoever BR. 2013. Influenza A virus utilizes suboptimal splicing to coordinate the timing of infection. Cell Rep 3:23-29. http://dx.doi.org/10.1016/j.celrep.2012.12.010.
19. Shih SR, Krug RM. 1996. Novel exploitation of a nuclear function by influenza virus: the cellular SF2/ASF splicing factor controls the amount of the essential viral M2 ion channel protein in infected cells. EMBO J 15: 5415-5427.
20. Shih SR, Nemeroff ME, Krug RM. 1995. The choice of alternative 5' splice sites in influenza virus M1 mRNA is regulated by the viral polymerase complex. Proc Natl Acad Sci U S A 92:6324-6328. http://dx.doi.org/10.1073/pnas.92.14.6324.
21. Robb NC, Fodor E. 2012. The accumulation of influenza A virus segment 7 spliced mRNAs is regulated by the NS1 protein. J Gen Virol 93:113-118. http://dx.doi.org/10.1099/vir.0.035485-0.
22. van Wielink R, Harmsen MM, Martens DE, Peeters BP, Wijffels RH, Moormann RJ. 2012. Mutations in the M-gene segment can substantially increase replication efficiency of NS1 deletion influenza A virus in MDCK cells. J Virol 86:12341-12350. http://dx.doi.org/10.1128/JVI.01725-12.
23. Hale BG, Randall RE, Ortin J, Jackson D. 2008. The multifunctional NS1 protein of influenza A viruses. J Gen Virol 89:2359-2376. http://dx.doi.org/10.1099/vir.0.2008/004606-0.
24. Krug RM. 2015. Functions of the influenza A virus NS1 protein in antiviral defense. Curr Opin Virol 12C:1-6.
25. Garcia-Sastre A, Egorov A, Matassov D, Brandt S, Levy DE, Durbin JE, Palese P, Muster T. 1998. Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252:324-330. http://dx.doi.org/10.1006/viro.1998.9508.
26. Egorov A, Brandt S, Sereinig S, Romanova J, Ferko B, Katinger D, Grassauer A, Alexandrova G, Katinger H, Muster T. 1998. Transfectant influenza A viruses with long deletions in the NS1 protein grow efficiently in Vero cells. J Virol 72:6437-6441.
27. Mok BW, Song W, Wang P, Tai H, Chen Y, Zheng M, Wen X, Lau SY, Wu WL, Matsumoto K, Yuen KY, Chen H. 2012. The NS1 protein of influenza A virus interacts with cellular processing bodies and stress granules through RNA-associated protein 55 (RAP55) during virus infection. J Virol 86:12695-12707. http://dx.doi.org/10.1128/JVI.00647-12.
28. Wen X, Huang X, Mok BW, Chen Y, Zheng M, Lau SY, Wang P, Song W, Jin DY, Yuen KY, Chen H. 2014. NF90 exerts antiviral activity through regulation of PKR phosphorylation and stress granules in infected cells. J Immunol 192:3753-3764. http://dx.doi.org/10.4049/jimmunol.1302813.
29. Song W, Wang P, Mok BW, Lau SY, Huang X, Wu WL, Zheng M, Wen X, Yang S, Chen Y, Li L, Yuen KY, Chen H. 2014. The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication. Nat Commun 5:5509. http://dx.doi.org/10.1038/ncomms6509.
30. Hoffmann E, Neumann G, Kawaoka Y, Hobom G, Webster RG. 2000. A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci U S A 97:6108-6113. http://dx.doi.org/10.1073/pnas.100133697.
31. Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402-408. http://dx.doi.org/10.1006/meth.2001.1262.
32. Kistner O, Barrett PN, Mundt W, Reiter M, Schober-Bendixen S, Dorner F. 1998. Development of a mammalian cell (Vero) derived candidate influenza virus vaccine. Vaccine 16:960-968. http://dx.doi.org/10.1016/S0264-410X(97)00301-0.
33. van Wielink R, Harmsen MM, Martens DE, Peeters BP, Wijffels RH, Moormann RJ. 2011. MDCK cell line with inducible allele B NS1 expression propagates delNS1 influenza virus to high titres. Vaccine 29:6976-6985. http://dx.doi.org/10.1016/j.vaccine.2011.07.037.
34. Chiang C, Chen GW, Shih SR. 2008. Mutations at alternative 5' splice sites of M1 mRNA negatively affect influenza A virus viability and growth rate. J Virol 82:10873-10886. http://dx.doi.org/10.1128/JVI.00506-08.
35. Enami M, Enami K. 2000. Characterization of influenza virus NS1 protein by using a novel helper-virus-free reverse genetic system. J Virol 74: 5556-5561. http://dx.doi.org/10.1128/JVI.74.12.5556-5561.2000.
36. Ichinohe T, Pang IK, Iwasaki A. 2010. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol 11:404-410. http://dx.doi.org/10.1038/ni.1861.
37. Gannage M, Dormann D, Albrecht R, Dengjel J, Torossi T, Ramer PC, Lee M, Strowig T, Arrey F, Conenello G, Pypaert M, Andersen J, Garcia-Sastre A, Munz C. 2009. Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes. Cell Host Microbe 6:367-380. http://dx.doi.org/10.1016/j.chom.2009.09.005.
38. Paterson D, Fodor E. 2012. Emerging roles for the influenza A virus nuclear export protein (NEP). PLoS Pathog 8:e1003019. http://dx.doi.org/10.1371/journal.ppat.1003019.
39. Dubois J, Terrier O, Rosa-Calatrava M. 2014. Influenza viruses and mRNA splicing: doing more with less. mBio 5(3):e00070-00014. http://dx.doi.org/10.1128/mBio.00070-14.
40. Manz B, Brunotte L, Reuther P, Schwemmle M. 2012. Adaptive mutations in NEP compensate for defective H5N1 RNA replication in cultured human cells. Nat Commun 3:802. http://dx.doi.org/10.1038/ncomms1804.
41. Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM. 1998. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell 1:991-1000. http://dx.doi.org/10.1016/S1097-2765(00)80099-4.
42. Garaigorta U, Ortin J. 2007. Mutation analysis of a recombinant NS replicon shows that influenza virus NS1 protein blocks the splicing and nucleo-cytoplasmic transport of its own viral mRNA. Nucleic Acids Res 35:4573-4582. http://dx.doi.org/10.1093/nar/gkm230.
43. Salvatore M, Basler CF, Parisien JP, Horvath CM, Bourmakina S, Zheng H, Muster T, Palese P, Garcia-Sastre A. 2002. Effects of influenza A virus NS1 protein on protein expression: the NS1 protein enhances translation and is not required for shutoff of host protein synthesis. J Virol 76:1206-1212. http://dx.doi.org/10.1128/JVI.76.3.1206-1212.2002.
44. Fernandez-Sesma A, Marukian S, Ebersole BJ, Kaminski D, Park MS, Yuen T, Sealfon SC, Garcia-Sastre A, Moran TM. 2006. Influenza virus evades innate and adaptive immunity via the NS1 protein. J Virol 80: 6295-6304. http://dx.doi.org/10.1128/JVI.02381-05.
45. Pica N, Langlois RA, Krammer F, Margine I, Palese P. 2012. NS1-truncated live attenuated virus vaccine provides robust protection to aged mice from viral challenge. J Virol 86:10293-10301. http://dx.doi.org/10.1128/JVI.01131-12.
46. Mueller SN, Langley WA, Carnero E, Garcia-Sastre A, Ahmed R. 2010. Immunization with live attenuated influenza viruses that express altered NS1 proteins results in potent and protective memory CD8 T-cell responses. J Virol 84:1847-1855. http://dx.doi.org/10.1128/JVI.01317-09.
47. Talon J, Salvatore M, O'Neill RE, Nakaya Y, Zheng H, Muster T, Garcia-Sastre A, Palese P. 2000. Influenza A and B viruses expressing altered NS1 proteins: a vaccine approach. Proc Natl Acad Sci U S A 97: 4309-4314. http://dx.doi.org/10.1073/pnas.070525997.
48. Richt JA, Garcia-Sastre A. 2009. Attenuated influenza virus vaccines with modified NS1 proteins. Curr Top Microbiol Immunol 333:177-195. http://dx.doi.org/10.1007/978-3-540-92165-3_9.
49. Wacheck V, Egorov A, Groiss F, Pfeiffer A, Fuereder T, Hoeflmayer D, Kundi M, Popow-Kraupp T, Redlberger-Fritz M, Mueller CA, Cinatl J, Michaelis M, Geiler J, Bergmann M, Romanova J, Roethl E, Morokutti A, Wolschek M, Ferko B, Seipelt J, Dick-Gudenus R, Muster T. 2010. A novel type of influenza vaccine: safety and immunogenicity of replicationdeficient influenza virus created by deletion of the interferon antagonist NS1. J Infect Dis 201:354-362. http://dx.doi.org/10.1086/649428.
50. Wressnigg N, Voss D, Wolff T, Romanova J, Ruthsatz T, Mayerhofer I, Reiter M, Nakowitsch S, Humer J, Morokutti A, Muster T, Egorov A, Kittel C. 2009. Development of a live-attenuated influenza B DeltaNS1 intranasal vaccine candidate. Vaccine 27:2851-2857. http://dx.doi.org/10.1016/j.vaccine.2009.02.087.
51. Kochs G, Martinez-Sobrido L, Lienenklaus S, Weiss S, Garcia-Sastre A, Staeheli P. 2009. Strong interferon-inducing capacity of a highly virulent variant of influenza A virus strain PR8 with deletions in the NS1 gene. J Gen Virol 90:2990-2994. http://dx.doi.org/10.1099/vir.0.015727-0.