H5N1禽流感病毒蛋白对1F1TM基因家族转录的影响
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摘要
干扰素诱导的跨膜蛋白(Interferon induced transmembrane protein,简称IFITM)通过抑制病毒进入细胞来保护细胞,使其免受多种病毒的感染。为了鉴定H5N1病毒本身和结构蛋白是否作为IFITM基因的新调节因子,通过试验探讨了H5N1病毒和结构蛋白对IFITM基因家族转录的影响。结果显示,H5N1病毒的NS1、M1、NP和PB2蛋白在A549细胞中增加了IFITM1、IFITM2和IFITM3表达,对HEK293T细胞没有影响,在HEK293T细胞和A549细胞上,没有发现H5N1病毒的HA和NA蛋白影响IFITM基因家族表达。即在H5N1禽流感病毒感染期间,NS1、M1、NP和PB2蛋白的过表达可以直接刺激IFITM1、IFITM2和IFITM3的上调,而呼吸系统的上皮细胞可能首先被影响,特别地,NP和NS1显示对IFITM基因家族的表达显示更显著的作用。
The interferon-induced transmembrane(IFITM) proteins usually protect cells from a variety of viruses by inhibiting their entry into them. In order to identify whether the H5 N1 virus itself and structural proteins act as a new regulator of IFITM gene, it investigates the effect of H5 N1 virus and structural proteins on IFITM gene family transcription through experiments. The results show that the NS1, M1, NP and PB2 proteins of H5 N1 virus increases the expressions of IFITM1, IFITM2 and IFITM3 in A549 cell, and has no effect on HEK293 T cell. No HA and NA proteins of H5 N1 virus were found to affect the IFITM gene family expression in HEK293 T cell and A549 cell. That is, during the infection of H5 N1 avian influenza virus, the overexpression of NS1, M1, NP and PB2 protein can directly stimulate the up-regulation of IFITM1, IFITM2 and IFITM3. While the respiratory epithelial cells may be affected first, in particular, NP and NS1 showed a more significant effect on the IFITM gene family expression.
The interferon-induced transmembrane(IFITM) proteins usually protect cells from a variety of viruses by inhibiting their entry into them. In order to identify whether the H5 N1 virus itself and structural proteins act as a new regulator of IFITM gene, it investigates the effect of H5 N1 virus and structural proteins on IFITM gene family transcription through experiments. The results show that the NS1, M1, NP and PB2 proteins of H5 N1 virus increases the expressions of IFITM1, IFITM2 and IFITM3 in A549 cell, and has no effect on HEK293 T cell. No HA and NA proteins of H5 N1 virus were found to affect the IFITM gene family expression in HEK293 T cell and A549 cell. That is, during the infection of H5 N1 avian influenza virus, the overexpression of NS1, M1, NP and PB2 protein can directly stimulate the up-regulation of IFITM1, IFITM2 and IFITM3. While the respiratory epithelial cells may be affected first, in particular, NP and NS1 showed a more significant effect on the IFITM gene family expression.
引文
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[25]Ye Z,Liu T,Offringa D P,etc.Association of Influenza Virus Matrix Protein with Ribonucleoproteins[J].Journal of Virology,1999,73:7 467-7 473.
[26]Digard P,Elton D,Bishop K,etc.Modulation of nuclear localization of the influenza virus nucleoprotein through interaction with actin filaments[J].Journal of Virology,1999,73:173-200.
[27]O'Neill R E,Palese P.NPI-1,the human homolog of SRP-1,interacts with influenza virus nucleoprotein[J].Virology,1995,206:116-125.
[28]Elton D,Simpsonholley M,Archer K,etc.Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway[J].Journal of Virology,2001,75:408-419.
[29]Momose F,Basler C F,O'Neill R E,etc.Cellular splicing factor RAF-2p48/NPI-5/BAT1/UAP56 interacts with the influenza virus nucleoprotein and enhances viral RNA synthesis[J].Journal of Virology,2001,75:1 899-1 908.
[2]刘宇虎,钟东,张振书,等.大肠癌中干扰素诱导的跨膜蛋白-1基因表达及其临床意义[J].中华消化杂志,2006,26(4):276-277.
[3]马娅梅,吴保平,夏欧东.干扰素诱导的跨膜蛋白1在Peutz-Jeghers综合征的表达及意义[J].南方医科大学学报,2009,29(3):541-543.
[4]何敬东,张振书,肖冰,等.干扰素诱导跨膜蛋白1协同干扰素抑制结肠癌细胞增殖[J].肿瘤,2006,26(8):705-707.
[5]Huang I C,Benita Y,John S P,etc.The IFITMProteins Mediate Cellular Resistance to Influenza AH1N1 Virus,West Nile Virus,and Dengue Virus[J].Cell,2009,139:1 243-1 254.
[6]Feeley E M,Sims J S,John S P,etc.IFITM3 inhibits influenza A virus infection by preventing cytosolic entry[J].Plos Pathogens,2011(7):337-337.
[7]Chan Y K,Huang I C,Farzan M.IFITM proteins restrict antibody-dependent enhancement of dengue virus infection[J].Plos One,2012(7):4 508-4 508.
[8]Lu J,Pan Q,Rong L,etc.The IFITM Proteins Inhibit HIV-1 Infection[J].Journal of Virology,2011,85:2 126-2 137.
[9]Bailey C C,Huang I,Kam C,etc.Ifitm3 Limits the Severity of Acute Influenza in Mice[J].Plos Pathogens,2012(8):244-251.
[10]Wang Y,Tong X,Ye X.Ndfip1 negatively regulates RIG-I-dependent immune signaling by enhancing E3ligase Smurf1-mediated MAVS degradation[J].Journal of Immunology,2012,189:5 304-5 313.
[11]Bailey C C,Zhong G,Huang IC,etc.IFITM-Family Proteins:The Cell's First Line of Antiviral Defense[J].Virology,2014(1):261-283.
[12]Friedman,Richard L,Manly,etc.Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells[J].Cell,1984,38:745-755.
[13]John S P,Chin C R,Perreira J M,etc.The CD225 Domain of IFITM3 Is Required for both I-FITM Protein Association and Inhibition of Influenza A Virus and Dengue Virus Replication[J].Journal of Virology,2013,87:7 837-7 852.
[14]Blyth G A,Chan W F,Webster R G,etc.Duck Interferon-Inducible Transmembrane Protein 3 Mediates Restriction of Influenza Viruses[J].Journal of Virology,2015,90:2 769-2 782.
[15]Schmitt A P,Lamb R A.Influenza Virus Assembly and Budding at the Viral Budozone[J].Advances in Virus Research,2005,64:383-416.
[16]Wu C Y,Jeng K S,Lai M M.The SUMOylation of matrix protein M1 modulates the assembly and morphogenesis of influenza A virus[J].Journal of Virology,2011,85:6 618-6 628.
[17]Fouchier R A,Munster V,Wallensten A,etc.Characterization of a Novel Influenza A Virus Hemagglutinin Subtype(H16)Obtained from Black-Headed Gulls[J].Journal of Virology,2005,79:2 814-2 822.
[18]Tong S,Li Y,Rivailler P,etc.A distinct lineage of influenza A virus from bats[J].Proceedings of the National Academy of Sciences,2012,109:4 269-4 274.
[19]Kobasa D,Takada A,Shinya K,etc.Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus[J].Australian Veterinary Journal,2004,431:703-707.
[20]Kash J C,Basler C F,Garcíasastre A,etc.Global host immune response:pathogenesis and transcriptional profiling of type A influenza viruses expressing the hemagglutinin and neuraminidase genes from the 1918pandemic virus[J].Journal of Virology,2004,78:9 499-9 511.
[21]Watanabe T,Tisoncikgo J,Tchitchek N,etc.1918Influenza virus hemagglutinin(HA)and the viral RNA polymerase complex enhance viral pathogenicity,but only HA induces aberrant host responses in mice[J].Journal of Virology,2013,87:5 239-5 254.
[22]Hale B,Randall R,Ortin J.The multifunctional NS1protein of influenza A viruses[J].Journal of General Virology,2008,89:2 359-2 376.
[23]Kochs G,Garcíasastre A,Martínezsobrido L.Multiple anti-interferon actions of the influenza A virus NS1protein[J].Journal of Virology,2007,81:7 011-7 021.
[24]Biswas S K,Boutz P L,Nayak D P.Influenza virus nucleoprotein interacts with influenza virus polymerase proteins[J].Journal of Virology,1998,72:5 493-5 501.
[25]Ye Z,Liu T,Offringa D P,etc.Association of Influenza Virus Matrix Protein with Ribonucleoproteins[J].Journal of Virology,1999,73:7 467-7 473.
[26]Digard P,Elton D,Bishop K,etc.Modulation of nuclear localization of the influenza virus nucleoprotein through interaction with actin filaments[J].Journal of Virology,1999,73:173-200.
[27]O'Neill R E,Palese P.NPI-1,the human homolog of SRP-1,interacts with influenza virus nucleoprotein[J].Virology,1995,206:116-125.
[28]Elton D,Simpsonholley M,Archer K,etc.Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway[J].Journal of Virology,2001,75:408-419.
[29]Momose F,Basler C F,O'Neill R E,etc.Cellular splicing factor RAF-2p48/NPI-5/BAT1/UAP56 interacts with the influenza virus nucleoprotein and enhances viral RNA synthesis[J].Journal of Virology,2001,75:1 899-1 908.
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