Search tips
Search criteria 


Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. 1993 April; 67(4): 2168–2174.
PMCID: PMC240327

An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif.


Spodoptera frugiperda SF-21 cells infected with Autographa californica nuclear polyhedrosis virus mutants which lack a functional p35 gene undergo apoptosis, a type of programmed cell death. To identify p35-homologous genes in other baculoviruses, A. californica nuclear polyhedrosis virus DNA containing a deletion in p35 was cotransfected into SF-21 cells along with genomic DNAs from other baculoviruses. One of the viral DNAs which were able to rescue wild-type infection was from Cydia pomonella granulosis virus (CpGV). The CpGV gene responsible for the effect was mapped to a 1.6-kb SalI-SstI subclone of the SalI B fragment of CpGV. The sequence of the SalI-SstI subclone revealed an open reading frame capable of encoding a polypeptide of 31 kDa which was sufficient to rescue wild-type infection; this gene was thus called iap (inhibitor of apoptosis). The predicted sequence of the IAP polypeptide exhibited no significant homology to P35 but contained a zinc finger-like motif which is also found in other genes with the potential to regulate apoptosis, including several mammalian proto-oncogenes and two insect genes involved in embryonic development. In the context of the viral genome, both iap and p35 were able to block apoptosis induced by actinomycin D, indicating that these genes act by blocking cellular apoptosis rather than by preventing viral stimulation of apoptosis. Several independent recombinant viruses derived from cotransfections with either the entire CpGV genome or the 1.6-kb subclone were characterized.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Blake TJ, Shapiro M, Morse HC, 3rd, Langdon WY. The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif. Oncogene. 1991 Apr;6(4):653–657. [PubMed]
  • Blissard GW, Quant-Russell RL, Rohrmann GF, Beaudreau GS. Nucleotide sequence, transcriptional mapping, and temporal expression of the gene encoding p39, a major structural protein of the multicapsid nuclear polyhedrosis virus of Orgyia pseudotsugata. Virology. 1989 Feb;168(2):354–362. [PubMed]
  • Braunagel SC, Daniel KD, Reilly LM, Guarino LA, Hong T, Summers MD. Sequence, genomic organization of the EcoRI-A fragment of Autographa californica nuclear polyhedrosis virus, and identification of a viral-encoded protein resembling the outer capsid protein VP8 of rotavirus. Virology. 1992 Dec;191(2):1003–1008. [PubMed]
  • Brunk BP, Martin EC, Adler PN. Drosophila genes Posterior Sex Combs and Suppressor two of zeste encode proteins with homology to the murine bmi-1 oncogene. Nature. 1991 Sep 26;353(6342):351–353. [PubMed]
  • Carson DD, Summers MD, Guarino LA. Molecular analysis of a baculovirus regulatory gene. Virology. 1991 May;182(1):279–286. [PubMed]
  • Carstens EB, Tjia ST, Doerfler W. Infection of Spodoptera frugiperda cells with Autographa californica nuclear polyhedrosis virus I. Synthesis of intracellular proteins after virus infection. Virology. 1979 Dec;99(2):386–398. [PubMed]
  • Clem RJ, Fechheimer M, Miller LK. Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science. 1991 Nov 29;254(5036):1388–1390. [PubMed]
  • de Thé H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A. The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell. 1991 Aug 23;66(4):675–684. [PubMed]
  • Devereux J, Haeberli P, Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. [PMC free article] [PubMed]
  • Freemont PS, Hanson IM, Trowsdale J. A novel cysteine-rich sequence motif. Cell. 1991 Feb 8;64(3):483–484. [PubMed]
  • Handermann M, Schnitzler P, Rösen-Wolff A, Raab K, Sonntag KC, Darai G. Identification and mapping of origins of DNA replication within the DNA sequences of the genome of insect iridescent virus type 6. Virus Genes. 1992 Jan;6(1):19–32. [PubMed]
  • Haupt Y, Alexander WS, Barri G, Klinken SP, Adams JM. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Cell. 1991 May 31;65(5):753–763. [PubMed]
  • Hershberger PA, Dickson JA, Friesen PD. Site-specific mutagenesis of the 35-kilodalton protein gene encoded by Autographa californica nuclear polyhedrosis virus: cell line-specific effects on virus replication. J Virol. 1992 Sep;66(9):5525–5533. [PMC free article] [PubMed]
  • Hink WF. Established insect cell line from the cabbage looper, Trichoplusia ni. Nature. 1970 May 2;226(5244):466–467. [PubMed]
  • Kakizuka A, Miller WH, Jr, Umesono K, Warrell RP, Jr, Frankel SR, Murty VV, Dmitrovsky E, Evans RM. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991 Aug 23;66(4):663–674. [PubMed]
  • Knauf VC, Nester EW. Wide host range cloning vectors: a cosmid clone bank of an Agrobacterium Ti plasmid. Plasmid. 1982 Jul;8(1):45–54. [PubMed]
  • Krappa R, Knebel-Mörsdorf D. Identification of the very early transcribed baculovirus gene PE-38. J Virol. 1991 Feb;65(2):805–812. [PMC free article] [PubMed]
  • Martin SJ, Lennon SV, Bonham AM, Cotter TG. Induction of apoptosis (programmed cell death) in human leukemic HL-60 cells by inhibition of RNA or protein synthesis. J Immunol. 1990 Sep 15;145(6):1859–1867. [PubMed]
  • Miller LK. Construction of a Genetic Map of the Baculovirus Autographa californica Nuclear Polyhedrosis Virus by Marker Rescue of Temperature-Sensitive Mutants. J Virol. 1981 Sep;39(3):973–976. [PMC free article] [PubMed]
  • Ooi BG, Miller LK. Regulation of host RNA levels during baculovirus infection. Virology. 1988 Oct;166(2):515–523. [PubMed]
  • Shimozawa N, Tsukamoto T, Suzuki Y, Orii T, Shirayoshi Y, Mori T, Fujiki Y. A human gene responsible for Zellweger syndrome that affects peroxisome assembly. Science. 1992 Feb 28;255(5048):1132–1134. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Summers MD, Smith GE, Knell JD, Burand JP. Physical Maps of Autographa californica and Rachiplusia ou Nuclear Polyhedrosis Virus Recombinants. J Virol. 1980 Jun;34(3):693–703. [PMC free article] [PubMed]
  • Tagawa M, Sakamoto T, Shigemoto K, Matsubara H, Tamura Y, Ito T, Nakamura I, Okitsu A, Imai K, Taniguchi M. Expression of novel DNA-binding protein with zinc finger structure in various tumor cells. J Biol Chem. 1990 Nov 15;265(32):20021–20026. [PubMed]
  • Takahashi M, Cooper GM. ret transforming gene encodes a fusion protein homologous to tyrosine kinases. Mol Cell Biol. 1987 Apr;7(4):1378–1385. [PMC free article] [PubMed]
  • Theilmann DA, Stewart S. Molecular analysis of the trans-activating IE-2 gene of Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus. Virology. 1992 Mar;187(1):84–96. [PubMed]
  • Theilmann DA, Stewart S. Tandemly repeated sequence at the 3' end of the IE-2 gene of the baculovirus Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus is an enhancer element. Virology. 1992 Mar;187(1):97–106. [PubMed]
  • Thiem SM, Miller LK. A baculovirus gene with a novel transcription pattern encodes a polypeptide with a zinc finger and a leucine zipper. J Virol. 1989 Nov;63(11):4489–4497. [PMC free article] [PubMed]
  • van Lohuizen M, Frasch M, Wientjens E, Berns A. Sequence similarity between the mammalian bmi-1 proto-oncogene and the Drosophila regulatory genes Psc and Su(z)2. Nature. 1991 Sep 26;353(6342):353–355. [PubMed]
  • Vaughn JL, Goodwin RH, Tompkins GJ, McCawley P. The establishment of two cell lines from the insect Spodoptera frugiperda (Lepidoptera; Noctuidae). In Vitro. 1977 Apr;13(4):213–217. [PubMed]
  • Walker NI, Harmon BV, Gobé GC, Kerr JF. Patterns of cell death. Methods Achiev Exp Pathol. 1988;13:18–54. [PubMed]
  • Williams GT, Smith CA, Spooncer E, Dexter TM, Taylor DR. Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature. 1990 Jan 4;343(6253):76–79. [PubMed]
  • Wirth UV, Fraefel C, Vogt B, Vlcek C, Paces V, Schwyzer M. Immediate-early RNA 2.9 and early RNA 2.6 of bovine herpesvirus 1 are 3' coterminal and encode a putative zinc finger transactivator protein. J Virol. 1992 May;66(5):2763–2772. [PMC free article] [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)