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Journal of Virology, November 2009, p. 11645-11654, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01110-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Contribution of Matrix, Fusion, Hemagglutinin, and Large Protein Genes of the CAM-70 Measles Virus Vaccine Strain to Efficient Growth in Chicken Embryonic Fibroblasts{triangledown}

Luna Bhatta Sharma,1 Shinji Ohgimoto,1* Seiichi Kato,1 Sekiko Kurazono,1 Minoru Ayata,1 Kaoru Takeuchi,2 Toshiaki Ihara,3 and Hisashi Ogura1

Department of Virology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, Osaka 545-8585, Japan,1 Department of Infection Biology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan,2 Department of Pediatrics, National Mie Hospital, 357 Osatokubota-cho, Tsu, Mie 514-0125, Japan3

Received 1 June 2009/ Accepted 23 August 2009

Attenuated live vaccines of measles virus (MV) have been developed from clinical isolates by serial propagation in heterologous cells, mainly chicken embryonic cells. The safety and effectiveness of these vaccines have been well established. However, the molecular mechanism of their attenuation remains a subject of investigation. The CAM-70 MV vaccine strain was developed from the Tanabe strain by serial propagation in chicken embryonic cells. In the present study, we assessed the contribution of each gene in the CAM-70 strain to efficient growth in chicken embryonic fibroblasts (CEF). We used a cloned MV IC323 based on the wild-type IC-B strain and generated a series of IC323s that possess one or more of the CAM-70 genes. Then, we examined the infection of CEF and CEF expressing human signaling lymphocyte activation molecule with the recombinant MVs. Our results demonstrated that MV needs to adapt to CEF at both the entry and postentry steps and that the CAM-70 matrix protein gene plays an important role in adaptation to CEF at the early stage of the virus replication cycle. The CAM-70 large protein gene was responsible for the efficient transcription and replication in CEF, and the CAM-70 hemagglutinin and fusion protein genes were responsible for efficient entry. Investigations focusing on these genes might elucidate unknown molecular mechanisms underlying the attenuation of MV.

* Corresponding author. Mailing address: Department of Virology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. Phone: 81-6-6645-3911. Fax: 81-6-6645-3912. E-mail: ohgimoto{at}med.osaka-cu.ac.jp

{triangledown} Published ahead of print on 2 September 2009.

Journal of Virology, November 2009, p. 11645-11654, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01110-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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