期刊论文详细信息
Virology Journal
Polymerase activity of hybrid ribonucleoprotein complexes generated from reassortment between 2009 pandemic H1N1 and seasonal H3N2 influenza A viruses
Paul KS Chan2  Karry LK Ngai1  Wai Y Lam1 
[1] Department of Microbiology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administration Region, People's Republic of China;Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administration Region, People's Republic of China
关键词: Pathogenesis;    RNA polymerase;    RNP;    NP;    PA;    PB2;    PB1;    Seasonal;    Pandemic;    Human swine influenza;   
Others  :  1155549
DOI  :  10.1186/1743-422X-8-528
 received in 2011-08-31, accepted in 2011-12-12,  发布年份 2011
PDF
【 摘 要 】

Background

A novel influenza virus (2009 pdmH1N1) was identified in early 2009 and progressed to a pandemic in mid-2009. This study compared the polymerase activity of recombinant viral ribonucleoprotein (vRNP) complexes derived from 2009 pdmH1N1 and the co-circulating seasonal H3N2, and their possible reassortants.

Results

The 2009 pdmH1N1 vRNP showed a lower level of polymerase activity at 33°C compared to 37°C, a property remenisence of avian viruses. The 2009 pdmH1N1 vRNP was found to be more cold-sensitive than the WSN or H3N2 vRNP. Substituion of 2009 pdmH1N1 vRNP with H3N2-derived-subunits, and vice versa, still retained a substantial level of polymerase activity, which is probably compartable with survival. When the 2009 pdmH1N1 vRNP was substituted with H3N2 PA, a significant increase in activity was observed; whereas when H3N2 vRNP was substituted with 2009 pdmH1N1 PA, a significant decrease in activity occurred. Although, the polymerase basic protein 2 (PB2) of 2009 pdmH1N1 was originated from an avian virus, substitution of this subunit with H3N2 PB2 did not change its polymerase activity in human cells.

Conclusions

In conclusion, our data suggest that hybrid vRNPs resulted from reassortment between 2009 pdmH1N1 and H3N2 viruses could still retain a substantial level of polymerase activity. Substituion of the subunit PA confers the most prominent effect on polymerase activity. Further studies to explore the determinants for polymerase activity of influenza viruses in associate with other factors that limit host specificity are warrant.

【 授权许可】

   
2011 Lam et al; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150407114816831.pdf 359KB PDF download
Figure 4. 36KB Image download
Figure 3. 42KB Image download
Figure 2. 39KB Image download
Figure 1. 24KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Centers for Disease Control and Prevention (CDC): Update: novel influenza A (H1N1) virus infection--Mexico March-May, 2009. MMWR Morb Mortal Wkly Rep 2009, 58:585-589.
  • [2]Itoh Y, Shinya K, Kiso M, Watanabe T, Sakoda Y, Hatta M, Muramoto Y, Tamura D, Sakai-Tagawa Y, Noda T, et al.: In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 2009, 460:1021-1025.
  • [3]Kashiwagi T, Hara K, Nakazono Y, Hamada N, Watanabe H: Artificial hybrids of influenza A virus RNA polymerase reveal PA subunit modulates its thermal sensitivity. PLoS One 2010, 5:e15140.
  • [4]Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM: Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009, 360:2605-2615.
  • [5]Peiris JS, Poon LL, Guan Y: Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans. J Clin Virol 2009, 45:169-173.
  • [6]Centers for Disease Control and Prevention (CDC): Update: novel influenza A (H1N1) virus infections--orldwide, May 6, 2009. In MMWR Morb Mortal Wkly Rep. Volume 58. 2009; :453-458.
  • [7]World Health Organization (WHO) 2010. Pandemic (H1N1) 2009[http://wwwwhoint/csr/disease/swineflu/en/indexhtml] webcite
  • [8]Beare AS, Webster RG: Replication of avian influenza viruses in humans. Arch Virol 1991, 119:37-42.
  • [9]Hatta M, Halfmann P, Wells K, Kawaoka Y: Human influenza a viral genes responsible for the restriction of its replication in duck intestine. Virology 2002, 295:250-255.
  • [10]Murphy BR, Sly DL, Tierney EL, Hosier NT, Massicot JG, London WT, Chanock RM, Webster RG, Hinshaw VS: Reassortant virus derived from avian and human influenza A viruses is attenuated and immunogenic in monkeys. Science 1982, 218:1330-1332.
  • [11]Abdel-Ghafar AN, Chotpitayasunondh T, Gao Z, Hayden FG, Nguyen DH, de Jong MD, Naghdaliyev A, Peiris JS, Shindo N, Soeroso S, et al.: Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med 2008, 358:261-273.
  • [12]Hatta M, Gao P, Halfmann P, Kawaoka Y: Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 2001, 293:1840-1842.
  • [13]Leung BW, Chen H, Brownlee GG: Correlation between polymerase activity and pathogenicity in two duck H5N1 influenza viruses suggests that the polymerase contributes to pathogenicity. Virology 2010, 401:96-106.
  • [14]Palese P, Shaw ML: Orthomyxoviridae: the viruses and their replication. In Fields Virology. 5th edition. Edited by Knipe DM, Howley RM. Philadelphia, PA: Lippincott Williams & Wilkins; 1647-1689.
  • [15]Dias A, Bouvier D, Crepin T, McCarthy AA, Hart DJ, Baudin F, Cusack S, Ruigrok RW: The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 2009, 458:914-918.
  • [16]Hara K, Shiota M, Kido H, Ohtsu Y, Kashiwagi T, Iwahashi J, Hamada N, Mizoue K, Tsumura N, Kato H, et al.: Influenza virus RNA polymerase PA subunit is a novel serine protease with Ser624 at the active site. Genes Cells 2001, 6:87-97.
  • [17]Hara K, Schmidt FI, Crow M, Brownlee GG: Amino acid residues in the N-terminal region of the PA subunit of influenza A virus RNA polymerase play a critical role in protein stability, endonuclease activity, cap binding, and virion RNA promoter binding. J Virol 2006, 80:7789-7798.
  • [18]Obayashi E, Yoshida H, Kawai F, Shibayama N, Kawaguchi A, Nagata K, Tame JR, Park SY: The structural basis for an essential subunit interaction in influenza virus RNA polymerase. Nature 2008, 454:1127-1131.
  • [19]Yuan P, Bartlam M, Lou Z, Chen S, Zhou J, He X, Lv Z, Ge R, Li X, Deng T, et al.: Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site. Nature 2009, 458:909-913.
  • [20]Fodor E, Crow M, Mingay LJ, Deng T, Sharps J, Fechter P, Brownlee GG: A single amino acid mutation in the PA subunit of the influenza virus RNA polymerase inhibits endonucleolytic cleavage of capped RNAs. J Virol 2002, 76:8989-9001.
  • [21]Maier HJ, Kashiwagi T, Hara K, Brownlee GG: Differential role of the influenza A virus polymerase PA subunit for vRNA and cRNA promoter binding. Virology 2008, 370:194-204.
  • [22]Li ML, Ramirez BC, Krug RM: RNA-dependent activation of primer RNA production by influenza virus polymerase: different regions of the same protein subunit constitute the two required RNA-binding sites. EMBO J 1998, 17:5844-5852.
  • [23]Li ML, Rao P, Krug RM: The active sites of the influenza cap-dependent endonuclease are on different polymerase subunits. EMBO J 2001, 20:2078-2086.
  • [24]Gonzalez S, Ortin J: Distinct regions of influenza virus PB1 polymerase subunit recognize vRNA and cRNA templates. EMBO J 1999, 18:3767-3775.
  • [25]Jung TE, Brownlee GG: A new promoter-binding site in the PB1 subunit of the influenza A virus polymerase. J Gen Virol 2006, 87:679-688.
  • [26]Fechter P, Mingay L, Sharps J, Chambers A, Fodor E, Brownlee GG: Two aromatic residues in the PB2 subunit of influenza A RNA polymerase are crucial for cap binding. J Biol Chem 2003, 278:20381-20388.
  • [27]Guilligay D, Tarendeau F, Resa-Infante P, Coloma R, Crepin T, Sehr P, Lewis J, Ruigrok RW, Ortin J, Hart DJ, et al.: The structural basis for cap binding by influenza virus polymerase subunit PB2. Nat Struct Mol Biol 2008, 15:500-506.
  • [28]Labadie K, Dos Santos AE, Rameix-Welti MA, van der WS, Naffakh N: Host-range determinants on the PB2 protein of influenza A viruses control the interaction between the viral polymerase and nucleoprotein in human cells. Virology 2007, 362:271-282.
  • [29]Subbarao EK, London W, Murphy BR: A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol 1993, 67:1761-1764.
  • [30]Gabriel G, Dauber B, Wolff T, Planz O, Klenk HD, Stech J: The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc Natl Acad Sci USA 2005, 102:18590-18595.
  • [31]Li Z, Chen H, Jiao P, Deng G, Tian G, Li Y, Hoffmann E, Webster RG, Matsuoka Y, Yu K: Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J Virol 2005, 79:12058-12064.
  • [32]Lee N, Chan PK, Lam WY, Szeto CC, Hui DS: Co-infection with pandemic H1N1 and seasonal H3N2 influenza viruses. Ann Intern Med 2010, 152:618-619.
  • [33]Brownlee GG, Sharps JL: The RNA polymerase of influenza a virus is stabilized by interaction with its viral RNA promoter. J Virol 2002, 76:7103-7113.
  • [34]Kashiwagi T, Leung BW, Deng T, Chen H, Brownlee GG: The N-terminal region of the PA subunit of the RNA polymerase of influenza A/HongKong/156/97 (H5N1) influences promoter binding. PLoS One 2009, 4:e5473.
  • [35]Song MS, Pascua PN, Lee JH, Baek YH, Park KJ, Kwon HI, Park SJ, Kim CJ, Kim H, Webby RJ, et al.: Virulence and Genetic Compatibility of Polymerase Reassortant Viruses Derived from the Pandemic (H1N1) 2009 Influenza Virus and Circulating Influenza A Viruses. J Virol 2011, 85:6275-6286.
  • [36]Le QM, Sakai-Tagawa Y, Ozawa M, Ito M, Kawaoka Y: Selection of H5N1 influenza virus PB2 during replication in humans. J Virol 2009, 83:5278-5281.
  • [37]Manzoor R, Sakoda Y, Nomura N, Tsuda Y, Ozaki H, Okamatsu M, Kida H: PB2 protein of a highly pathogenic avian influenza virus strain A/chicken/Yamaguchi/7/2004 (H5N1) determines its replication potential in pigs. J Virol 2009, 83:1572-1578.
  • [38]Mase M, Tanimura N, Imada T, Okamatsu M, Tsukamoto K, Yamaguchi S: Recent H5N1 avian influenza A virus increases rapidly in virulence to mice after a single passage in mice. J Gen Virol 2006, 87:3655-3659.
  • [39]Steel J, Lowen AC, Mubareka S, Palese P: Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627 K or 627E/701 N. PLoS Pathog 2009, 5:e1000252.
  • [40]Subbarao K, Klimov A, Katz J, Regnery H, Lim W, Hall H, Perdue M, Swayne D, Bender C, Huang J, et al.: Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 1998, 279:393-396.
  • [41]Gonzalez S, Zurcher T, Ortin J: Identification of two separate domains in the influenza virus PB1 protein involved in the interaction with the PB2 and PA subunits: a model for the viral RNA polymerase structure. Nucleic Acids Res 1996, 24:4456-4463.
  • [42]Ohtsu Y, Honda Y, Sakata Y, Kato H, Toyoda T: Fine mapping of the subunit binding sites of influenza virus RNA polymerase. Microbiol Immunol 2002, 46:167-175.
  • [43]Sugiyama K, Obayashi E, Kawaguchi A, Suzuki Y, Tame JR, Nagata K, Park SY: Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase. EMBO J 2009, 28:1803-1811.
  • [44]Hemerka JN, Wang D, Weng Y, Lu W, Kaushik RS, Jin J, Harmon AF, Li F: Detection and characterization of influenza A virus PA-PB2 interaction through a bimolecular fluorescence complementation assay. J Virol 2009, 83:3944-3955.
  • [45]Fodor E, Devenish L, Engelhardt OG, Palese P, Brownlee GG, Garcia-Sastre A: Rescue of influenza A virus from recombinant DNA. J Virol 1999, 73:9679-9682.
  文献评价指标  
  下载次数:20次 浏览次数:16次