This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Jesus, D. M.
Right arrow Articles by Damaso, C. R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jesus, D. M.
Right arrow Articles by Damaso, C. R.

 Previous Article  |  Next Article 

Journal of Virology, November 2009, p. 11477-11490, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01061-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cidofovir Inhibits Genome Encapsidation and Affects Morphogenesis during the Replication of Vaccinia Virus{triangledown}

Desyreé Murta Jesus,1 Lilian T. Costa,3 Daniela L. Gonçalves,3 Carlos Alberto Achete,3,4 Marcia Attias,2 Nissin Moussatché,1,5 and Clarissa R. Damaso1*

Laboratório de Biologia Molecular de Vírus,1 Laboratório de Ultraestrutura Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho,2 Engenharia Metalúrgica e de Materiais, Universidade Federal do Rio de Janeiro, Rio de Janeiro,4 Divisão de Metrologia de Materiais, Inmetro, Duque de Caxias, Brazil,3 Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida5

Received 24 May 2009/ Accepted 26 August 2009

Cidofovir (CDV) is one of the most effective antiorthopoxvirus drugs, and it is widely accepted that viral DNA replication is the main target of its activity. In the present study, we report a detailed analysis of CDV effects on the replicative cycles of distinct vaccinia virus (VACV) strains: Cantagalo virus, VACV-IOC, and VACV-WR. We show that despite the approximately 90% inhibition of production of virus progeny, virus DNA accumulation was reduced only 30%, and late gene expression and genome resolution were unaltered. The level of proteolytic cleavage of the major core proteins was diminished in CDV-treated cells. Electron microscopic analysis of virus-infected cells in the presence of CDV revealed reductions as great as 3.5-fold in the number of mature forms of virus particles, along with a 3.2-fold increase in the number of spherical immature particles. A detailed analysis of purified virions recovered from CDV-treated cells demonstrated the accumulation of unprocessed p4a and p4b and nearly 67% inhibition of DNA encapsidation. However, these effects of CDV on virus morphogenesis resulted from a primary effect on virus DNA synthesis, which led to later defects in genome encapsidation and virus assembly. Analysis of virus DNA by atomic force microscopy revealed that viral cytoplasmic DNA synthesized in the presence of CDV had an altered structure, forming aggregates with increased strand overlapping not observed in the absence of the drug. These aberrant DNA aggregations were not encapsidated into virus particles.

* Corresponding author. Mailing address: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil. Phone: 55 (21) 2562-6510. Fax: 55 (21) 2280-8193. E-mail: damasoc{at}biof.ufrj.br

{triangledown} Published ahead of print on 2 September 2009.

Journal of Virology, November 2009, p. 11477-11490, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01061-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»