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Journal of Virology, June 2003, p. 6419-6429, Vol. 77, No. 11
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.11.6419-6429.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A New Sendai Virus Vector Deficient in the Matrix Gene Does Not Form Virus Particles and Shows Extensive Cell-to-Cell Spreading

Makoto Inoue,1* Yumiko Tokusumi,1 Hiroshi Ban,1 Takumi Kanaya,1 Masayuki Shirakura,1 Tsuyoshi Tokusumi,1 Takahiro Hirata,1 Yoshiyuki Nagai,2 Akihiro Iida,1 and Mamoru Hasegawa1

DNAVEC Research Inc., Tsukuba-shi, Ibaraki 305-0856,1 Toyama Institute of Health, Kosugi-machi, Imizu-gun, Toyama 939-0363, Japan2

Received 29 October 2002/ Accepted 13 February 2003

A new recombinant Sendai virus vector (SeV/{Delta}M), in which the gene encoding matrix (M) protein was deleted, was recovered from cDNA and propagated in a packaging cell line expressing M protein by using a Cre/loxP induction system. The titer of SeV/{Delta}M carrying the enhanced green fluorescent protein gene in place of the M gene was 7 x 107 cell infectious units/ml or more. The new vector showed high levels of infectivity and gene expression, similar to those of wild-type SeV vector, in vitro and in vivo. Virus maturation into a particle was almost completely abolished in cells infected with SeV/{Delta}M. Instead, SeV/{Delta}M infection brought about a significant increase of syncytium formation under conditions in which the fusion protein was proteolytically cleaved and activated by trypsin-like protease. This shows that SeV/{Delta}M spreads markedly to neighboring cells in a cell-to-cell manner, because both hemagglutinin-neuraminidase and active fusion proteins are present at very high levels on the surface of cells infected with SeV/{Delta}M. Thus, SeV/{Delta}M is a novel type of vector with the characteristic features of loss of virus particle formation and gain of cell-to-cell spreading via a mechanism dependent on the activation of the fusion protein.

* Corresponding author. Mailing address: 1-25-11 Kannondai, Tsukuba-shi, Ibaraki 305-0856, Japan. Phone: 81-29-838-0540. Fax: 81-29-839-1123. E-mail: inoue{at}dnavec.co.jp.

Journal of Virology, June 2003, p. 6419-6429, Vol. 77, No. 11
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.11.6419-6429.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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