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Accommodation of foreign genes into the Sendai virus genome: sizes of inserted genes and viral replication
Author(s) -
Sakai Yuko,
Kiyotani Katsuhiro,
Fukumura Masayuki,
Asakawa Makoto,
Kato Atsushi,
Shioda Tatsuo,
Yoshida Tetsuya,
Tanaka Akemi,
Hasegawa Mamoru,
Nagai Yoshiyuki
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00960-6
Subject(s) - sendai virus , biology , gene , viral replication , virus , insert (composites) , genome , genetics , origin of replication , virology , complementary dna , microbiology and biotechnology , mechanical engineering , engineering
Sendai virus (SeV) is an enveloped virus with a negative sense genome RNA of about 15.3 kb. We previously established a system to recover an infectious virus entirely from SeV cDNA and illustrated the feasibility of using SeV as a novel expression vector. Here, we have attempted to insert a series of foreign genes into SeV of different lengths to learn how far SeV can accommodate extra genes and how the length of inserted genes affects viral replication in cells cultured in vitro and in the natural host, mice. We show that a gene up to 3.2 kb can be inserted and efficiently expressed and that the replication speed as well as the final virus titers in cell culture are proportionally reduced as the inserted gene length increases. In vivo, such a size‐dependent effect was not very clear but a remarkably attenuated replication and pathogenicity were generally seen. Our data further confirmed reinforcement of foreign gene expression in vitro from the V(−) version of SeV in which the accessory V gene had been knocked out. Based on these results, we discuss the utility of SeV vector in terms of both efficiency and safety.