Leishmania (Viannia) braziliensis transfectants overexpressing the miniexon gene lose virulence in vivo

Autor(es)

de Toledo, Juliano Simoes ^[1] ; Junqueira dos Santos, Andre F. ^[1] ; de Moura, Tatiana Rodrigues ^[2] ; Antoniazi, Simone Aparecida ^[1] ; Brodskyn, Claudia ^{[2, 3]} ; de Oliveira, Camila Indiani ^[2] ; Barral, Aldina ^{[2, 3]} ; Cruz, Angela Kaysel ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Fiocruz MS, Ctr Pesquisas Goncalo Moniz, Salvador, BA - Brazil

^[3] Inst Invest Imunol, Salvador, BA - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Parasitology International; v. 58, n. 1, p. 45-50, Mar. 2009.
• Área do conhecimento: Ciências Biológicas - Bioquímica
• Citações Web of Science: 6
• Assunto(s): Protozoa Leishmania braziliensis Virulência RNA não traduzido RNA líder para processamento

Resumo

The miniexon gene has a central role in the processing of polycistronic pre-mRNA of kinetoplastids. It is added to the 5' extremity of each mRNA, supplying the 5'-capped structure to the molecule. Previous studies in Leishmania (Leishmania) major showed that the overexpression of the miniexon array attenuates the virulence of the parasite in in vivo assays. The results presented here extend those findings to Viannia subgenus. Leishmania (Viannia) braziliensis was transfected with a cosmid harboring a tandem array of one hundred miniexon gene copies and then characterized by Northern blot analysis. The overexpression of the exogenous gene was confirmed and its effect on the virulence of L. (V.) braziliensis was investigated in hamsters. In BALB/c mice we could not detect parasites during the course of 15 weeks of infection. In addition, hamsters infected with transfectants overexpressing the miniexon gene exhibited only a minor footpad swelling of late onset and failed to develop progressive lesion, these attenuated parasites could be recovered from the inoculation site 1 year after infection. The persistence of parasites in the host indicates that a stable line overexpressing the miniexon may be tested as live vaccine against leishmaniasis. (AU)

• Processo FAPESP: 03/02366-0 - Miniexon e virulencia em leishmania major.
• Beneficiário: Juliano Simões de Toledo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 99/12403-3 - Do genoma à biologia de Leishmania: uma abordagem compreensiva
• Beneficiário: Angela Kaysel Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 06/50323-7 - Estudo do controle da expressão gênica e plasticidade genética em Leishmania
• Beneficiário: Angela Kaysel Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Temático