Important note: Information in this article was accurate in August 2003. The state of the art may have changed since the publication date. |
AIDSWEEKLY Plus; Monday, August 4, 2003
Michael Greer, Senior Medical Writer
Highly attenuated MVA "serves as a candidate vaccine to immunize against infectious diseases and cancer," including HIV infection, explained Simone Hornemann and colleagues at Ludwig Maximilians University in Munich and the Technical University of Munich.
A mutant form of MVA lacking expression of the IFN resistance gene E3L was unable to replicate in chicken embryo fibroblasts (CEF) used in experimental tissue cultures, Hornemann and coauthors found.
The researchers developed an MVA deletion mutant dubbed MVA-deltaE3L. This mutant did not have the ability to grow in CEF, a functional loss that was reversed by reinsertion of the missing E3L gene, according to the report.
DNA replication of MVA-deltaE3L was seen during nonproductive CEF infection, but viral protein synthesis was incomplete and infected cells underwent rapid apoptosis, study data showed. In additon, CEF infected with mutant MVA produced high levels of interferon (IFN)-alpha and -beta.
Further tests showed that elevated levels of IFN-alpha may underlie the defective growth of mutant MVA in CEF (Replication of modified vaccinia virus Ankara in primary chicken embryo fibroblasts requires expression of the interferon resistance gene E3L. J Virol. 2003 Aug;77(15):8394-407.
Hornemann and colleagues concluded that "efficient propagation of MVA in CEF, the tissue culture system used for production of MVA-based vaccines, essentially requires conserved E3L gene function as an inhibitor of apoptosis and/or IFN induction."
The corresponding author for this report is Gerd Sutter, GSF-Institut fuer Molekulare Virologie, Trogerstr. 4b, 81675 Munich, Germany. E-mail: sutter@gsf.de.
Key points reported in this study include:
The interferon resistance gene E3L is needed for the growth of modified vaccinia virus Ankara (MVA) in chicken embryo fibroblasts (CEF)
Mutant MVA lacking this gene was unable to replicate in CEF
This effect may be due to the elevated interferon-alpha production seen from CEF infected with mutant MVA
This article was prepared by AIDS Weekly editors from staff and other reports.
Reference
Hornemann S, Harlin O, Staib C, et al., "Replication of modified vaccinia virus Ankara in primary chicken embryo fibroblasts requires expression of the interferon resistance gene E3L", J Virol. 2003 Aug;77(15):8394-407.
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