Gene optimization leads to robust expression of human respiratory syncytial virus nucleoprotein and phosphoprotein in human cells and induction of humoral immunity in mice

Autor(es)

Simabuco, Fernando M. ^[1] ; Tamura, Rodrigo E. ^[1] ; Carromeu, Cassiano ^[1] ; Farinha-Arcieri, Luis E. ^[1] ; Ventura, Armando M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Virological Methods; v. 158, n. 1-2, p. 93-99, JUN 2009.
• Citações Web of Science: 4

Resumo

Human respiratory syncytial virus (HRSV) is the major pathogen leading to respiratory disease in infants and neonates worldwide. An effective vaccine has not yet been developed against this virus, despite considerable efforts in basic and clinical research. HRSV replication is independent of the nuclear RNA processing constraints, since the virus genes are adapted to the cytoplasmic transcription, a process performed by the viral RNA-dependent RNA polymerase. This study shows that meaningful nuclear RNA polymerase II dependent expression of the HRSV nucleoprotein (N) and phosphoprotein (F) proteins can only be achieved with the optimization of their genes, and that the intracellular localization of N and P proteins changes when they are expressed out of the virus replication context. Immunization tests performed in mice resulted in the induction of humoral immunity using the optimized genes. This result was not observed for the non-optimized genes. In conclusion, optimization is a valuable tool for improving expression of HRSV genes in DNA vaccines. (c) 2009 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 03/02041-4 - Expressao de proteinas e peptideos de rsv e hiv para estudos moleculares e de imunizacao.
• Beneficiário: Armando Morais Ventura
• Modalidade de apoio: Auxílio à Pesquisa - Regular