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J Virol. 1994 April; 68(4): 2521–2528.
PMCID: PMC236730

An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs.


Two different baculovirus genes are known to be able to block apoptosis triggered upon infection of Spodoptera frugiperda cells with p35 mutants of the insect baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV):p35 (P35-encoding gene) of AcMNPV (R. J. Clem, M. Fechheimer, and L. K. Miller, Science 254:1388-1390, 1991) and iap (inhibitor of apoptosis gene) of Cydia pomonella granulosis virus (CpGV) (N. E. Crook, R. J. Clem, and L. K. Miller, J. Virol. 67:2168-2174, 1993). Using a genetic complementation assay to identify additional genes which inhibit apoptosis during infection with a p35 mutant, we have isolated a gene from Orgyia pseudotsugata NPV (OpMNPV) that was able to functionally substitute for AcMNPV p35. The nucleotide sequence of this gene, Op-iap, predicted a 30-kDa polypeptide product with approximately 58% amino acid sequence identity to the product of CpGV iap, Cp-IAP. Like Cp-IAP, the predicted product of Op-iap has a carboxy-terminal C3HC4 zinc finger-like motif. In addition, a pair of additional cysteine/histidine motifs were found in the N-terminal regions of both polypeptide sequences. Recombinant p35 mutant viruses carrying either Op-iap or Cp-iap appeared to have a normal phenotype in S. frugiperda cells. Thus, Cp-IAP and Op-IAP appear to be functionally analogous to P35 but are likely to block apoptosis by a different mechanism which may involve direct interaction with DNA.

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Selected References

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  • Blissard GW, Rohrmann GF. Baculovirus diversity and molecular biology. Annu Rev Entomol. 1990;35:127–155. [PubMed]
  • Chou J, Roizman B. The gamma 1(34.5) gene of herpes simplex virus 1 precludes neuroblastoma cells from triggering total shutoff of protein synthesis characteristic of programed cell death in neuronal cells. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3266–3270. [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]
  • Clem RJ, Miller LK. Apoptosis reduces both the in vitro replication and the in vivo infectivity of a baculovirus. J Virol. 1993 Jul;67(7):3730–3738. [PMC free article] [PubMed]
  • Crook NE, Clem RJ, Miller LK. An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J Virol. 1993 Apr;67(4):2168–2174. [PMC free article] [PubMed]
  • Debbas M, White E. Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B. Genes Dev. 1993 Apr;7(4):546–554. [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]
  • Friesen PD, Miller LK. Divergent transcription of early 35- and 94-kilodalton protein genes encoded by the HindIII K genome fragment of the baculovirus Autographa californica nuclear polyhedrosis virus. J Virol. 1987 Jul;61(7):2264–2272. [PMC free article] [PubMed]
  • Gombart AF, Blissard GW, Rohrmann GF. Characterization of the genetic organization of the HindIII M region of the multicapsid nuclear polyhedrosis virus of Orgyia pseudotsugata reveals major differences among baculoviruses. J Gen Virol. 1989 Jul;70(Pt 7):1815–1828. [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]
  • Henderson S, Rowe M, Gregory C, Croom-Carter D, Wang F, Longnecker R, Kieff E, Rickinson A. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell. 1991 Jun 28;65(7):1107–1115. [PubMed]
  • Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. [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]
  • Hockenbery D, Nuñez G, Milliman C, Schreiber RD, Korsmeyer SJ. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334–336. [PubMed]
  • Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 1991 Dec 1;51(23 Pt 1):6304–6311. [PubMed]
  • Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491–7495. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Leisy DJ, Rohrmann GF, Beaudreau GS. Conservation of genome organization in two multicapsid nuclear polyhedrosis viruses. J Virol. 1984 Nov;52(2):699–702. [PMC free article] [PubMed]
  • Levine B, Huang Q, Isaacs JT, Reed JC, Griffin DE, Hardwick JM. Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature. 1993 Feb 25;361(6414):739–742. [PubMed]
  • Maltzman W, Czyzyk L. UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells. Mol Cell Biol. 1984 Sep;4(9):1689–1694. [PMC free article] [PubMed]
  • Marchini A, Tomkinson B, Cohen JI, Kieff E. BHRF1, the Epstein-Barr virus gene with homology to Bc12, is dispensable for B-lymphocyte transformation and virus replication. J Virol. 1991 Nov;65(11):5991–6000. [PMC free article] [PubMed]
  • Martin JM, Veis D, Korsmeyer SJ, Sugden B. Latent membrane protein of Epstein-Barr virus induces cellular phenotypes independently of expression of Bcl-2. J Virol. 1993 Sep;67(9):5269–5278. [PMC free article] [PubMed]
  • Neilan JG, Lu Z, Afonso CL, Kutish GF, Sussman MD, Rock DL. An African swine fever virus gene with similarity to the proto-oncogene bcl-2 and the Epstein-Barr virus gene BHRF1. J Virol. 1993 Jul;67(7):4391–4394. [PMC free article] [PubMed]
  • Price BD, Chang Z, Smith R, Bockheim S, Laughon A. The Drosophila neuralized gene encodes a C3HC4 zinc finger. EMBO J. 1993 Jun;12(6):2411–2418. [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]
  • 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]
  • Vaux DL, Weissman IL, Kim SK. Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2. Science. 1992 Dec 18;258(5090):1955–1957. [PubMed]
  • White E, Sabbatini P, Debbas M, Wold WS, Kusher DI, Gooding LR. The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor alpha. Mol Cell Biol. 1992 Jun;12(6):2570–2580. [PMC free article] [PubMed]

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