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https://hdl.handle.net/1822/63071
Título: | A method for the generation of ectromelia virus (ECTV) recombinants: in vivo analysis of ECTV vCD30 deletion mutants |
Autor(es): | Alejo, Ali Saraiva, Margarida Ruiz-Argüello, Maria Begoña Viejo-Borbolla, Abel de Marco, Mar Fernández Salguero, Francisco Javier Alcami, Antonio |
Palavras-chave: | Animals Cell Line Disease Progression Ectromelia virus Ectromelia, Infectious Female Humans Ki-1 Antigen Ligands Mice Mice, Inbred BALB C Protein Multimerization Viral Proteins Virus Replication Mutation Recombination, Genetic |
Data: | 2009 |
Editora: | Public Library of Science (PLOS) |
Revista: | PLoS ONE |
Resumo(s): | Background: Ectromelia virus (ECTV) is the causative agent of mousepox, a lethal disease of mice with similarities to human smallpox. Mousepox progression involves replication at the initial site of infection, usually the skin, followed by a rapid spread to the secondary replicative organs, spleen and liver, and finally a dissemination to the skin, where the typical rash associated with this and other orthopoxviral induced diseases appears. Case fatality rate is genetically determined and reaches up to 100% in susceptible mice strains. Like other poxviruses, ECTV encodes a number of proteins with immunomodulatory potential, whose role in mousepox progression remains largely undescribed. Amongst these is a secreted homologue of the cellular tumour necrosis factor receptor superfamily member CD30 which has been proposed to modulate a Th1 immune response in vivo. Methodology/Principal Findings: To evaluate the contribution of viral CD30 (vCD30) to virus pathogenesis in the infected host, we have adapted a novel transient dominant method for the selection of recombinant ECTVs. Using this method, we have generated an ECTV vCD30 deletion mutant, its corresponding revertant control virus as well as a virus encoding the extracellular domain of murine CD30. These viruses contain no exogenous marker DNA sequences in their genomes, as opposed to other ECTVs reported up to date. Conclusions/Significance: We show that the vCD30 is expressed as a secreted disulfide linked trimer and that the absence of vCD30 does not impair mousepox induced fatality in vivo. Replacement of vCD30 by a secreted version of mouse CD30 caused limited attenuation of ECTV. The recombinant viruses generated may be of use in the study of the role of the cellular CD30-CD30L interaction in the development of the immune response. The method developed might be useful for the construction of ECTV mutants for the study of additional genes. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/63071 |
DOI: | 10.1371/journal.pone.0005175 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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journal.pone.0005175.PDF | 1,1 MB | Adobe PDF | Ver/Abrir |