Identification of putative interactions between swine and human influenza A virus nucleoprotein and human host proteins

Virology Journal

Heidi Sleister¹  Marc Busch¹  Joseph Jacher¹  Jeff Barcus¹  Molly Thorson¹  Alex Generous¹ 

[1] Biology Department, Drake University, 1344 27th St., Des Moines 50311, IA, USA

关键词: Host restriction;    Yeast two-hybrid;    Nucleoprotein;    Influenza A virus;   

Others  :  1131063
DOI  :  10.1186/s12985-014-0228-6

 received in 2014-06-17, accepted in 2014-12-15,  发布年份 2014

【 摘 要 】

Background

Influenza A viruses (IAVs) are important pathogens that affect the health of humans and many additional animal species. IAVs are enveloped, negative single-stranded RNA viruses whose genome encodes at least ten proteins. The IAV nucleoprotein (NP) is a structural protein that associates with the viral RNA and is essential for virus replication. Understanding how IAVs interact with host proteins is essential for elucidating all of the required processes for viral replication, restrictions in species host range, and potential targets for antiviral therapies.

Methods

In this study, the NP from a swine IAV was cloned into a yeast two-hybrid “bait” vector for expression of a yeast Gal4 binding domain (BD)-NP fusion protein. This “bait” was used to screen a Y2H human HeLa cell “prey” library which consisted of human proteins fused to the Gal4 protein’s activation domain (AD). The interaction of “bait” and “prey” proteins resulted in activation of reporter genes.

Results

Seventeen positive bait-prey interactions were isolated in yeast. All of the “prey” isolated also interact in yeast with a NP “bait” cloned from a human IAV strain. Isolation and sequence analysis of the cDNAs encoding the human prey proteins revealed ten different human proteins. These host proteins are involved in various host cell processes and structures, including purine biosynthesis (PAICS), metabolism (ACOT13), proteasome (PA28B), DNA-binding (MSANTD3), cytoskeleton (CKAP5), potassium channel formation (KCTD9), zinc transporter function (SLC30A9), Na+/K+ ATPase function (ATP1B1), and RNA splicing (TRA2B).

Conclusions

Ten human proteins were identified as interacting with IAV NP in a Y2H screen. Some of these human proteins were reported in previous screens aimed at elucidating host proteins relevant to specific viral life cycle processes such as replication. This study extends previous findings by suggesting a mechanism by which these host proteins associate with the IAV, i.e., physical interaction with NP. Furthermore, this study revealed novel host protein-NP interactions in yeast.

【 授权许可】

   
2014 Generous et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Taubenberger JK, Morens DM: The pathology of influenza virus infections. Annu Rev Pathol 2008, 3:499-522.
• [2]Taubenberger JK, Morens, DM: 1918 Influenza: the Mother of All Pandemics.http://wwwnc.cdc.gov/eid/article/12/1/05-0979_article.htm (2006). Accessed 17 June 2014.
• [3](CDC) CfDCaP: Swine influenza A (H1N1) infection in two children--Southern California, March-April 2009 MMWR Morb Mortal Wkly Rep 2009, 58:400-402.
• [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]Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y: Evolution and ecology of influenza A viruses. Microbiol Rev 1992, 56:152-179.
• [6]Olsen CW: The emergence of novel swine influenza viruses in North America. Virus Res 2002, 85:199-210.
• [7]Vincent AL, Ma W, Lager KM, Janke BH, Richt JA: Swine influenza viruses a North American perspective. Adv Virus Res 2008, 72:127-154.
• [8]Skehel JJ, Wiley DC: Receptor binding and membrane fusion in virus entry: the influenza Hemagglutinin. Annu Rev Biochem 2000, 69:531-569.
• [9]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.
• [10]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 U S A 2005, 102:18590-18595.
• [11]Manz B, Schwemmle M, Brunotte L: Adaptation of avian influenza A virus polymerase in mammals to overcome the host species barrier. J Virol 2013, 87:7200-7209.
• [12]Portela A, Digard P: The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. J Gen Virol 2002, 83:723-734.
• [13]Marklund JK, Ye Q, Dong J, Tao YJ, Krug RM: Sequence in the influenza A virus nucleoprotein required for viral polymerase binding and RNA synthesis. J Virol 2012, 86:7292-7297.
• [14]Scholtissek C, Ludwig S, Fitch WM: Analysis of influenza A virus nucleoproteins for the assessment of molecular genetic mechanisms leading to new phylogenetic virus lineages. Arch Virol 1993, 131:237-250.
• [15]Xu J, Christman MC, Donis RO, Lu G: Evolutionary dynamics of influenza A nucleoprotein (NP) lineages revealed by large-scale sequence analyses. Infect Genet Evol 2011, 11:2125-2132.
• [16]Chen GW, Chang SC, Mok CK, Lo YL, Kung YN, Huang JH, Shih YH, Wang JY, Chiang C, Chen CJ, Shih SR: Genomic signatures of human versus avian influenza A viruses. Emerg Infect Dis 2006, 12:1353-1360.
• [17]Pan C, Cheung B, Tan S, Li C, Li L, Liu S, Jiang S: Genomic signature and mutation trend analysis of pandemic (H1N1) 2009 influenza A virus. PLoS One 2010, 5:e9549.
• [18]Gabriel G, Herwig A, Klenk HD: Interaction of polymerase subunit PB2 and NP with importin alpha1 is a determinant of host range of influenza A virus. PLoS Pathog 2008, 4:e11.
• [19]Digard P, Elton D, Bishop K, Medcalf E, Weeds A, Pope B: Modulation of nuclear localization of the influenza virus nucleoprotein through interaction with actin filaments. J Virol 1999, 73:2222-2231.
• [20]Wang P, Song W, Mok BW, Zhao P, Qin K, Lai A, Smith GJ, Zhang J, Lin T, Guan Y, Chen H: Nuclear factor 90 negatively regulates influenza virus replication by interacting with viral nucleoprotein. J Virol 2009, 83:7850-7861.
• [21]Wang Z, Liu X, Zhao Z, Xu C, Zhang K, Chen C, Sun L, Gao GF, Ye X, Liu W: Cyclophilin E functions as a negative regulator to influenza virus replication by impairing the formation of the viral ribonucleoprotein complex. PLoS One 2011, 6:e22625.
• [22]Elton D, Simpson-Holley M, Archer K, Medcalf L, Hallam R, McCauley J, Digard P: Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway. J Virol 2001, 75:408-419.
• [23]Moisy D, Avilov SV, Jacob Y, Laoide BM, Ge X, Baudin F, Naffakh N, Jestin JL: HMGB1 protein binds to influenza virus nucleoprotein and promotes viral replication. J Virol 2012, 86:9122-9133.
• [24]Turan K, Mibayashi M, Sugiyama K, Saito S, Numajiri A, Nagata K: Nuclear MxA proteins form a complex with influenza virus NP and inhibit the transcription of the engineered influenza virus genome. Nucleic Acids Res 2004, 32:643-652.
• [25]Verhelst J, Parthoens E, Schepens B, Fiers W, Saelens X: Interferon-inducible protein Mx1 inhibits influenza virus by interfering with functional viral ribonucleoprotein complex assembly. J Virol 2012, 86:13445-13455.
• [26]Sharma K, Tripathi S, Ranjan P, Kumar P, Garten R, Deyde V, Katz JM, Cox NJ, Lal RB, Sambhara S, Lal SK: Influenza A virus nucleoprotein exploits Hsp40 to inhibit PKR activation. PLoS One 2011, 6:e20215.
• [27]O’Neill RE, Palese P: NPI-1, the human homolog of SRP-1, interacts with influenza virus nucleoprotein. Virology 1995, 206:116-125.
• [28]Shapira SD, Gat-Viks I, Shum BOV, Dricot A, de Grace MM, Wu L, Gupta PB, Hao T, Silver SJ, Root DE: A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. Cell 2009, 139:1255-1267.
• [29]Tripathi S, Batra J, Cao W, Sharma K, Patel JR, Ranjan P, Kumar A, Katz JM, Cox NJ, Lal RB, Sambhara S, Lal SK: Influenza A virus nucleoprotein induces apoptosis in human airway epithelial cells: implications of a novel interaction between nucleoprotein and host protein Clusterin. Cell Death Dis 2013, 4:e562. doi:10.1038/cddis.2013.89
• [30]Momose F, Basler CF, O'Neill RE, Iwamatsu A, Palese P, Nagata K: Cellular splicing factor RAF-2p48/NPI-5/BAT1/UAP56 interacts with the influenza virus nucleoprotein and enhances viral RNA synthesis. J Virol 2001, 75:1899-1908.
• [31]Balasubramaniam VR, Hong Wai T, Ario Tejo B, Omar AR, Syed Hassan S: Highly pathogenic avian influenza virus nucleoprotein interacts with TREX complex adaptor protein Aly/REF. PLoS One 2013, 8:e72429.
• [32]Naito T, Kiyasu Y, Sugiyama K, Kimura A, Nakano R, Matsukage A, Nagata K: An influenza virus replicon system in yeast identified Tat-SF1 as a stimulatory host factor for viral RNA synthesis. Proc Natl Acad Sci U S A 2007, 104:18235-18240.
• [33]Di Pietro A, Kajaste-Rudnitski A, Oteiza A, Nicora L, Towers GJ, Mechti N, Vicenzi E: TRIM22 inhibits influenza A virus infection by targeting the viral nucleoprotein for degradation. J Virol 2013, 87:4523-4533.
• [34]Sharma S, Mayank AK, Nailwal H, Tripathi S, Patel JR, Bowzard JB, Gaur P, Donis RO, Katz JM, Cox NJ, Lal RB, Farooqi H, Sambhara S, Lal SK: Influenza A viral nucleoprotein interacts with cytoskeleton scaffolding protein alpha-actinin-4 for viral replication. FEBS J 2014, 281:2899-2914.
• [35]Bean WJ: Correlation of influenza A virus nucleoprotein genes with host species. Virology 1984, 133:438-442.
• [36]Scholtissek C, Burger H, Kistner O, Shortridge KF: The nucleoprotein as a possible major factor in determining host specificity of influenza H3N2 viruses. Virology 1985, 147:287-294.
• [37]Snyder MH, Buckler-White AJ, London WT, Tierney EL, Murphy BR: The avian influenza virus nucleoprotein gene and a specific constellation of avian and human virus polymerase genes each specify attenuation of avian-human influenza A/Pintail/79 reassortant viruses for monkeys. J Virol 1987, 61:2857-2863.
• [38]Brass AL, Huang I, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E: The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 2009, 139:1243-1254.
• [39]Hao L, Sakurai A, Watanabe T, Sorensen E, Nidom CA, Newton MA, Ahlquist P, Kawaoka Y: Drosophila RNAi screen identifies host genes important for influenza virus replication. Nature 2008, 454:890-893.
• [40]Karlas A, Machuy N, Shin Y, Pleissner K-P, Artarini A, Heuer D, Becker D, Khalil H, Ogilvie LA, Hess S: Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 2010, 463:818-822.
• [41]König R, Stertz S, Zhou Y, Inoue A, Hoffmann HH, Bhattacharyya S, Alamares JG, Tscherne DM, Ortigoza MB, Liang Y: Human host factors required for influenza virus replication. Nature 2009, 463:813-817.
• [42]Shaw ML, Stone KL, Colangelo CM, Gulcicek EE, Palese P: Cellular proteins in influenza virus particles. PLoS Pathog 2008, 4:e1000085.
• [43]Song J-M, Choi C-W, Kwon S-O, Compans RW, Kang S-M, Kim SI: Proteomic characterization of influenza H5N1 virus-like particles and their protective immunogenicity. J Proteome Res 2011, 10:3450-3459.
• [44]Sui B, Bamba D, Weng K, Ung H, Chang S, Van Dyke J, Goldblatt M, Duan R, Kinch MS, Li W-B: The use of random homozygous gene perturbation to identify novel host-oriented targets for influenza. Virology 2009, 387:473-481.
• [45]Fields S, Sternglanz R: The two-hybrid system: an assay for protein-protein interactions. Trends Genet 1994, 10:286-292.
• [46]Li S-X, Tong Y-P, Xie X-C, Wang Q-H, Zhou H-N, Han Y, Zhang Z-Y, Gao W, Li S-G, Zhang XC: Octameric structure of the human bifunctional enzyme PAICS in purine biosynthesis. J Mol Biol 2007, 366:1603-1614.
• [47]Kumar R, Nanduri B: HPIDB--a unified resource for host-pathogen interactions. BMC Bioinformatics 2010, 11(Suppl 6):S16-2105-2111-S2106-S2116. BioMed Central Full Text
• [48]Kroeker AL, Ezzati P, Coombs KM, Halayko AJ: Influenza A infection of primary human airway epithelial cells up-regulates proteins related to purine metabolism and ubiquitin-related signaling. J Proteome Res 2013, 12:3139-3151.
• [49]Kaplan JH: Biochemistry of Na, K-ATPase. Annu Rev Biochem 2002, 71:511-535.
• [50]Liu L, Zhou J, Wang Y, Mason RJ, Funk CJ, Du Y: Proteome alterations in primary human alveolar macrophages in response to influenza A virus infection. J Proteome Res 2012, 11:4091-4101.
• [51]Mi S, Li Y, Yan J, Gao GF: Na(+)/K (+)-ATPase beta1 subunit interacts with M2 proteins of influenza A and B viruses and affects the virus replication. Sci China Life Sci 2010, 53:1098-1105.
• [52]Falcón-Pérez JM, Dell'Angelica EC: Zinc transporter 2 (SLC30A2) can suppress the vesicular zinc defect of adaptor protein 3-depleted fibroblasts by promoting zinc accumulation in lysosomes. Exp Cell Res 2007, 313:1473-1483.
• [53]Liuzzi JP, Cousins RJ: Mammalian zinc transporters. Annu Rev Nutr 2004, 24:151-172.
• [54]Huang L, Tepaamorndech S: The SLC30 family of zinc transporters – a review of current understanding of their biological and pathophysiological roles. Mol Asp Med 2013, 34:548-560.
• [55]Elliott DJ, Best A, Dalgliesh C, Ehrmann I, Grellscheid S: How does Tra2β protein regulate tissue-specific RNA splicing?Biochem Soc Transact 2012, 40:784–788.
• [56]Zhu J, Zou W, Jia G, Zhou H, Hu Y, Peng M, Chen H, Jin M: Analysis of cellular proteome alterations in porcine alveolar macrophage cells infected with 2009 (H1N1) and classical swine H1N1 influenza viruses. J Proteome 2012, 75:1732-1741.
• [57]Kang HW, Niepel MW, Han S, Kawano Y, Cohen DE: Thioesterase superfamily member 2/acyl-CoA thioesterase 13 (Them2/Acot13) regulates hepatic lipid and glucose metabolism. FASEB J 2012, 26:2209-2221.
• [58]Wei J, Kang HW, Cohen DE: Thioesterase superfamily member 2 (Them2)/acyl-CoA thioesterase 13 (Acot13): a homotetrameric hotdog fold thioesterase with selectivity for long-chain fatty acyl-CoAs. Biochem J 2009, 421:311-322.
• [59]Brocker C, Carpenter C, Nebert DW, Vasiliou V: Evolutionary divergence and functions of the human acyl-CoA thioesterase gene (ACOT) family. Hum Genomics 2010, 4:411-420. BioMed Central Full Text
• [60]Cassimeris L, Becker B, Carney B: TOGp regulates microtubule assembly and density during mitosis and contributes to chromosome directional instability. Cell Motil Cytoskeleton 2009, 66:535-545.
• [61]Lakadamyali M, Rust MJ, Babcock HP, Zhuang X: Visualizing infection of individual influenza viruses. Proc Natl Acad Sci U S A 2003, 100:9280-9285.
• [62]Kosturko LD, Maggipinto MJ, D'Sa C, Carson JH, Barbarese E: The microtubule-associated protein tumor overexpressed gene binds to the RNA trafficking protein heterogeneous nuclear ribonucleoprotein A2. Mol Biol Cell 2005, 16:1938-1947.
• [63]Tai AW, Benita Y, Peng LF, Kim SS, Sakamoto N, Xavier RJ, Chung RT: A functional genomic screen identifies cellular cofactors of hepatitis C virus replication. Cell Host Microbe 2009, 5:298-307.
• [64]Skoblov M, Marakhonov A, Marakasova E, Guskova A, Chandhoke V, Birerdinc A, Baranova A: Protein partners of KCTD proteins provide insights about their functional roles in cell differentiation and vertebrate development. Bioessays 2013, 35:586-596.
• [65]Kang KW, Lee SJ, Park JW, Kim SG: Phosphatidylinositol 3-kinase regulates nuclear translocation of NF-E2-related factor 2 through actin rearrangement in response to oxidative stress. Mol Pharmacol 2002, 62:1001-1010.
• [66]Kesic MJ, Simmons SO, Bauer R, Jaspers I: Nrf2 expression modifies influenza A entry and replication in nasal epithelial cells. Free Radic Biol Med 2011, 51:444-453.
• [67]Kish-Trier E, Hill CP: Structural biology of the proteasome. Annu Rev Biophys 2013, 42:29-49.
• [68]Sijts A, Sun Y, Janek K, Kral S, Paschen A, Schadendorf D, Kloetzel P-M: The role of the proteasome activator PA28 in MHC class I antigen processing. Mol Immunol 2002, 39:165-169.
• [69]Codina A, Love JD, Li Y, Lazar MA, Neuhaus D, Schwabe JW: Structural insights into the interaction and activation of histone deacetylase 3 by nuclear receptor corepressors. Proc Natl Acad Sci U S A 2005, 102:6009-6014.
• [70]Baker AM, Fu Q, Hayward W, Lindsay SM, Fletcher TM: The Myb/SANT domain of the telomere-binding protein TRF2 alters chromatin structure. Nucleic Acids Res 2009, 37:5019-5031.
• [71]Kewitz S, Staege MS: Expression and regulation of the endogenous retrovirus 3 in Hodgkin’s lymphoma cells.Front Oncol 2013, 3:179. doi: 10.3389/fonc.2013.00179.
• [72]Engdahl C, Naslund J, Lindgren L, Ahlm C, Bucht G: The Rift Valley Fever virus protein NSm and putative cellular protein interactions. Virol J 2012, 9:139. BioMed Central Full Text