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Journal of Virology, November 2005, p. 14346-14354, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14346-14354.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Long Untranslated Regions of the Measles Virus M and F Genes Control Virus Replication and Cytopathogenicity

Makoto Takeda,* Shinji Ohno, Fumio Seki, Yuichiro Nakatsu, Maino Tahara, and Yusuke Yanagi

Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan

Received 24 May 2005/ Accepted 23 August 2005

Measles is still a major cause of mortality mainly in developing countries. The causative agent, measles virus (MeV), is an enveloped virus having a nonsegmented negative-sense RNA genome, and belongs to the genus Morbillivirus of the family Paramyxoviridae. One feature of the moribillivirus genomes is that the M and F genes have long untranslated regions (UTRs). The M and F mRNAs of MeV have 426-nucleotide-long 3' and 583-nucleotide-long 5' UTRs, respectively. Though these long UTRs occupy as much as ~6.4% of the virus genome, their function remains unknown. To elucidate the role of the long UTRs in the context of virus infection, we used the reverse genetics based on the virulent strain of MeV, and generated a series of recombinant viruses having alterations or deletions in the long UTRs. Our results showed that these long UTRs per se were not essential for MeV replication, but that they regulated MeV replication and cytopathogenicity by modulating the productions of the M and F proteins. The long 3' UTR of the M mRNA was shown to have the ability to increase the M protein production, promoting virus replication. On the other hand, the long 5' UTR of the F mRNA was found to possess the capacity to decrease the F protein production, inhibiting virus replication and yet greatly reducing cytopathogenicity. We speculate that the reduction in cytopathogenicity may be advantageous for MeV fitness and survival in nature.


* Corresponding author. Mailing address: Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan. Phone: 81-92-642-6138. Fax: 81-92-642-6140. E-mail: mtakeda{at}virology.med.kyushu-u.ac.jp.


Journal of Virology, November 2005, p. 14346-14354, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14346-14354.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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