Inhibition of Virus DNA Replication by Artificial Zinc Finger Proteins

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2005 Feb 1

PMID 15681461

Citations 34

Authors

Takashi Sera

Affiliations

Soon will be listed here.

Abstract

Prevention of virus infections is a major objective in agriculture and human health. One attractive approach to the prevention is inhibition of virus replication. To demonstrate this concept in vivo, an artificial zinc finger protein (AZP) targeting the replication origin of the Beet severe curly top virus (BSCTV), a model DNA virus, was created. In vitro DNA binding assays indicated that the AZP efficiently blocked binding of the viral replication protein (Rep), which initiates virus replication, to the replication origin. All of the transgenic Arabidopsis plants expressing the AZP showed phenotypes strongly resistant to virus infection, and 84% of the transgenic plants showed no symptom. Southern blot analysis demonstrated that BSCTV replication was completely suppressed in the transgenic plants. Since the mechanism of viral DNA replication is well conserved among plants and mammals, this approach could be applied not only to agricultural crop protection but also to the prevention of virus infections in humans.

Citing Articles

Geminivirus diseases of legumes in India: current status and approaches for management.

Kumar S, Chakravarty A, Sahoo L Physiol Mol Biol Plants. 2025; 31(1):41-65.

PMID: 39901958 PMC: 11787143. DOI: 10.1007/s12298-024-01531-9.

Geminiviruses and Food Security: A Molecular Genetics Perspective for Sustainable Agriculture in Africa.

Zenda M, Masamba P, Allie F, Kappo A Plants (Basel). 2024; 13(19).

PMID: 39409638 PMC: 11478365. DOI: 10.3390/plants13192768.

Advancing crop disease resistance through genome editing: a promising approach for enhancing agricultural production.

Manzoor S, Nabi S, Rather T, Gani G, Mir Z, Wani A Front Genome Ed. 2024; 6:1399051.

PMID: 38988891 PMC: 11234172. DOI: 10.3389/fgeed.2024.1399051.

LbCas12a mediated suppression of .

Ashraf S, Ahmad A, Khan S, Jamil A, Sadia B, Brown J Front Plant Sci. 2023; 14:1233295.

PMID: 37636103 PMC: 10456881. DOI: 10.3389/fpls.2023.1233295.

Natural and Engineered Resistance Mechanisms in Plants against Phytoviruses.

Majumdar A, Sharma A, Belludi R Pathogens. 2023; 12(4).

PMID: 37111505 PMC: 10143959. DOI: 10.3390/pathogens12040619.

References

Stanley J, Latham J . A symptom variant of beet curly top geminivirus produced by mutation of open reading frame C4. Virology. 1992; 190(1):506-9. DOI: 10.1016/0042-6822(92)91243-n. View

Deom C, Lapidot M, Beachy R . Plant virus movement proteins. Cell. 1992; 69(2):221-4. DOI: 10.1016/0092-8674(92)90403-y. View

Hormuzdi S, Bisaro D . Genetic analysis of beet curly top virus: evidence for three virion sense genes involved in movement and regulation of single- and double-stranded DNA levels. Virology. 1993; 193(2):900-9. DOI: 10.1006/viro.1993.1199. View

Frischmuth S, Frischmuth T, Latham J, Stanley J . Transcriptional analysis of the virion-sense genes of the geminivirus beet curly top virus. Virology. 1993; 197(1):312-9. DOI: 10.1006/viro.1993.1592. View

Lee S, Stenger D, Bisaro D, Davis K . Identification of loci in Arabidopsis that confer resistance to geminivirus infection. Plant J. 1994; 6(4):525-35. DOI: 10.1046/j.1365-313x.1994.6040525.x. View

Dickinson L, Gulizia R, Trauger J, BAIRD E, Mosier D, Gottesfeld J . Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands. Proc Natl Acad Sci U S A. 1998; 95(22):12890-5. PMC: 23643. DOI: 10.1073/pnas.95.22.12890. View

Clough S, Bent A . Floral dip: a simplified method for Agrobacterium-mediated transformation of Arabidopsis thaliana. Plant J. 1999; 16(6):735-43. DOI: 10.1046/j.1365-313x.1998.00343.x. View

Balzarini J, Naesens L, De Clercq E . New antivirals - mechanism of action and resistance development. Curr Opin Microbiol. 1999; 1(5):535-46. DOI: 10.1016/s1369-5274(98)80086-6. View

Tai T, Dahlbeck D, CLARK E, Gajiwala P, Pasion R, Whalen M . Expression of the Bs2 pepper gene confers resistance to bacterial spot disease in tomato. Proc Natl Acad Sci U S A. 1999; 96(24):14153-8. PMC: 24206. DOI: 10.1073/pnas.96.24.14153. View

10.

Orozco B, Kong L, Batts L, Elledge S, Hanley-Bowdoin L . The multifunctional character of a geminivirus replication protein is reflected by its complex oligomerization properties. J Biol Chem. 2000; 275(9):6114-22. DOI: 10.1074/jbc.275.9.6114. View

11.

Hanin M, Volrath S, Bogucki A, Briker M, Ward E, Paszkowski J . Gene targeting in Arabidopsis. Plant J. 2002; 28(6):671-7. DOI: 10.1046/j.1365-313x.2001.01183.x. View

12.

Sera T, Uranga C . Rational design of artificial zinc-finger proteins using a nondegenerate recognition code table. Biochemistry. 2002; 41(22):7074-81. DOI: 10.1021/bi020095c. View

13.

Reynolds L, Ullman C, Moore M, Isalan M, West M, Clapham P . Repression of the HIV-1 5' LTR promoter and inhibition of HIV-1 replication by using engineered zinc-finger transcription factors. Proc Natl Acad Sci U S A. 2003; 100(4):1615-20. PMC: 149881. DOI: 10.1073/pnas.252770699. View

14.

Jaag H, Kawchuk L, Rohde W, Fischer R, Emans N, Prufer D . An unusual internal ribosomal entry site of inverted symmetry directs expression of a potato leafroll polerovirus replication-associated protein. Proc Natl Acad Sci U S A. 2003; 100(15):8939-44. PMC: 166417. DOI: 10.1073/pnas.1332697100. View

15.

Tzfira T, Li J, Lacroix B, Citovsky V . Agrobacterium T-DNA integration: molecules and models. Trends Genet. 2004; 20(8):375-83. DOI: 10.1016/j.tig.2004.06.004. View

16.

Li J, Kelly T . Simian virus 40 DNA replication in vitro. Proc Natl Acad Sci U S A. 1984; 81(22):6973-7. PMC: 392058. DOI: 10.1073/pnas.81.22.6973. View

17.

Briddon R, Watts J, Markham P, Stanley J . The coat protein of beet curly top virus is essential for infectivity. Virology. 1989; 172(2):628-33. DOI: 10.1016/0042-6822(89)90205-5. View

18.

Stenger D, Carbonaro D, Duffus J . Genomic characterization of phenotypic variants of beet curly top virus. J Gen Virol. 1990; 71 ( Pt 10):2211-5. DOI: 10.1099/0022-1317-71-10-2211. View

19.

Stenger D, Revington G, Stevenson M, Bisaro D . Replicational release of geminivirus genomes from tandemly repeated copies: evidence for rolling-circle replication of a plant viral DNA. Proc Natl Acad Sci U S A. 1991; 88(18):8029-33. PMC: 52439. DOI: 10.1073/pnas.88.18.8029. View

20.

Stanley J, Latham J, Pinner M, Bedford I, Markham P . Mutational analysis of the monopartite geminivirus beet curly top virus. Virology. 1992; 191(1):396-405. DOI: 10.1016/0042-6822(92)90201-y. View