title: Upregulation of a novel eukaryotic translation initiation factor 5A (eIF5A) in dengue 2 virus-infected mosquito cells.
abstract: BACKGROUND
  Dengue virus, a mosquito-borne flavivirus, is the etiological agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. It generally induces apoptosis in mammalian cells, but frequently results in persistent infection in mosquito cells. That mechanism remains to be explored. In turn, a genomic survey through subtractive hybridization (PCR-select cDNA subtraction) was conducted in order to find gene(s) that may play a role in interactions between the virus and its host cells.
  
  
  RESULTS
  Through this technique, we identified a novel eukaryotic translation initiation factor 5A (eIF5A) which is upregulated in Aedes albopictus-derived C6/36 cells infected by the type 2 dengue (Den-2) virus. The full-length of the identified eIF5A gene consisted of 1498 bp of nucleotides with a 41.39% G+C content, and it possessed a higher similarity and shorter evolutionary distance with insects than with other organisms. Upregulation of eIF5A in response to Den-2 virus infection was validated at both the RNA and protein levels. This phenomenon was also observed by confocal microscopy. In addition, cell death obviously occurred when eIF5A activity was inhibited in C6/36 cells even when they were infected by the virus. However, viral multiplication was not obviously affected in infected C6/36 cells when eIF5A activity was reduced.
  
  
  CONCLUSIONS
  Taken together, we postulated that eIF5A plays a role in preventing mosquito cells from death in response to Den-2 viral infection, thus facilitating continued viral growth and potential persistent infection in mosquito cells. It would be worthwhile to further investigate how its downstream factors or cofactors contribute to this phenomenon of dengue infection.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Department of Public Health and Parasitology, Chang Gung University, Kwei-San, Tao-Yuan 33332, Taiwan.
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Shih
authors.forename: Chao-Fu
authors.initials: CF
authors.lastname: Yang
authors.forename: Wei-June
authors.initials: WJ
authors.lastname: Chen
mesh_terms: D000330:Aedes / Q000821:virology*; D000818:Animals; D001482:Base Composition; D016923:Cell Death; D002460:Cell Line; D003716:Dengue Virus / Q000254:growth & development*; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D019476:Insect Proteins / Q000096:biosynthesis* / Q000235:genetics; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D019476:Insect Proteins; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A
references.citation: Biochim Biophys Acta. 1990 Aug 27;1050(1-3):160-2
references.pmid: 2119810
references.citation: J Biol Chem. 1989 Nov 5;264(31):18527-30
references.pmid: 2509460
references.citation: J Eukaryot Microbiol. 2006 Mar-Apr;53(2):127-35
references.pmid: 16579815
references.citation: J Infect. 2010 Jan;60(1):65-75
references.pmid: 19837110
references.citation: Trends Biochem Sci. 1993 Dec;18(12):475-9
references.pmid: 8108861
references.citation: Intervirology. 1994;37(1):25-30
references.pmid: 7928286
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10829-33
references.pmid: 7971969
references.citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6554-9
references.pmid: 18451031
references.citation: J Virol. 2005 Nov;79(21):13218-30
references.pmid: 16227245
references.citation: Exp Cell Res. 1995 Jul;219(1):159-68
references.pmid: 7628532
references.citation: J Biol Chem. 2001 Jan 26;276(4):2555-61
references.pmid: 11060315
references.citation: Adv Virus Res. 2003;59:23-61
references.pmid: 14696326
references.citation: J Biol Chem. 1987 Dec 5;262(34):16585-9
references.pmid: 3119588
references.citation: J Virol. 2003 Nov;77(21):11822-32
references.pmid: 14557666
references.citation: J Virol. 1981 Jun;38(3):1015-24
references.pmid: 7241667
references.citation: J Virol. 2002 Nov;76(22):11254-64
references.pmid: 12388685
references.citation: Mol Biol Evol. 1994 Jan;11(1):65-71
references.pmid: 8121287
references.citation: Infect Immun. 2004 Jul;72(7):4114-26
references.pmid: 15213157
references.citation: Adv Virus Res. 2003;60:157-86
references.pmid: 14689694
references.citation: Arch Med Res. 2002 Jul-Aug;33(4):330-42
references.pmid: 12234522
references.citation: Trends Biochem Sci. 1998 Oct;23(10):403-5
references.pmid: 9810230
references.citation: J Biol Chem. 1994 Feb 11;269(6):3934-40
references.pmid: 8307948
references.citation: Biochem J. 2004 Dec 15;384(Pt 3):585-90
references.pmid: 15303967
references.citation: Mol Biol Evol. 2007 Aug;24(8):1596-9
references.pmid: 17488738
references.citation: Virus Res. 2007 Mar;124(1-2):176-83
references.pmid: 17156880
references.citation: Biochem Biophys Res Commun. 2000 May 19;271(3):559-64
references.pmid: 10814501
references.citation: Virology. 2001 Oct 10;289(1):129-36
references.pmid: 11601924
references.citation: J Mol Biol. 2000 Aug 25;301(4):759-67
references.pmid: 10966782
references.citation: Nature. 1995 May 25;375(6529):291-8
references.pmid: 7753193
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712