tetano
Editor, Senior Moderator
Vaccine. 2010 Aug 4. [Epub ahead of print]
Differential activation of host cell signalling pathways through infection with two variants of influenza A/PR/8/34 (H1N1) in MDCK cells.
Heynisch B, Frensing T, Heinze K, Seitz C, Genzel Y, Reichl U.
Chair of Bioprocess Engineering, Institute for Process Engineering, Otto von Guericke University, Universit?tsplatz 2, 39106 Magdeburg, Germany.
Abstract
In cell culture-based influenza vaccine production, few efforts have been undertaken to characterise virus-host cell interactions in detail. Two production strains that grew to different virus titres, and differed in virus dynamics, apoptosis induction and proteome changes were observed. In order to elucidate biological mechanisms related to these differences, the induction of signalling cascades in adherent MDCK cells infected with two variants of influenza A/PuertoRico/8/34 (H1N1) was analysed. The pathways chosen for analysis are key components of the innate immune response and crucial for influenza A virus replication (NF-kappaB, IRF-3, PI3K-Akt, Jak-Stat, Raf/MEK/ERK, PKR/eIF2alpha). Interestingly, all investigated pathways were induced stronger by PR8-NIBSC than by PR8-RKI, the virus variant which results in higher virus titres. In particular, PR8-NIBSC infection lead to a higher induction of IFN-beta as well as IFN-stimulated gene expression, which was confirmed by Western blot as well as real-time PCR. Overall, results obtained clearly facilitate interpretation of observations regarding proteome changes and virus-induced apoptosis in cell culture-based vaccine manufacturing processes and support efforts towards design of improved host cell lines. Copyright ? 2010. Published by Elsevier Ltd.
PMID: 20691654 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20691654
Differential activation of host cell signalling pathways through infection with two variants of influenza A/PR/8/34 (H1N1) in MDCK cells.
Heynisch B, Frensing T, Heinze K, Seitz C, Genzel Y, Reichl U.
Chair of Bioprocess Engineering, Institute for Process Engineering, Otto von Guericke University, Universit?tsplatz 2, 39106 Magdeburg, Germany.
Abstract
In cell culture-based influenza vaccine production, few efforts have been undertaken to characterise virus-host cell interactions in detail. Two production strains that grew to different virus titres, and differed in virus dynamics, apoptosis induction and proteome changes were observed. In order to elucidate biological mechanisms related to these differences, the induction of signalling cascades in adherent MDCK cells infected with two variants of influenza A/PuertoRico/8/34 (H1N1) was analysed. The pathways chosen for analysis are key components of the innate immune response and crucial for influenza A virus replication (NF-kappaB, IRF-3, PI3K-Akt, Jak-Stat, Raf/MEK/ERK, PKR/eIF2alpha). Interestingly, all investigated pathways were induced stronger by PR8-NIBSC than by PR8-RKI, the virus variant which results in higher virus titres. In particular, PR8-NIBSC infection lead to a higher induction of IFN-beta as well as IFN-stimulated gene expression, which was confirmed by Western blot as well as real-time PCR. Overall, results obtained clearly facilitate interpretation of observations regarding proteome changes and virus-induced apoptosis in cell culture-based vaccine manufacturing processes and support efforts towards design of improved host cell lines. Copyright ? 2010. Published by Elsevier Ltd.
PMID: 20691654 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20691654