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Journal of Virology, June 2008, p. 5359-5367, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.00169-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Attenuation of V- or C-Defective Measles Viruses: Infection Control by the Inflammatory and Interferon Responses of Rhesus Monkeys{triangledown}

Patricia Devaux,1 Gregory Hodge,2 Michael B. McChesney,2 and Roberto Cattaneo1*

Department of Molecular Medicine and Virology and Gene Therapy Graduate Track, Mayo Clinic College of Medicine, Rochester, Minnesota 55905,1 California National Primate Research Center and Department of Pathology and Laboratory Medicine, School of Medicine, University of California—Davis, Davis, California 956162

Received 24 January 2008/ Accepted 23 March 2008

Patients recruited in virus-based cancer clinical trials and immunocompromised individuals in need of vaccination would profit from viral strains with defined attenuation mechanisms. We generated measles virus (MV) strains defective for the expression of either the V protein, a modulator of the innate immune response, or the C protein, which has multiple functions. The virulence of these strains was compared with that of the parental wild-type MV in a natural host, Macaca mulatta. Skin rash, viremia, and the strength of the innate and adaptive immune responses were characterized in groups of six animals. Replication of V- or C-protein-defective viruses was short-lived and reached lower levels in peripheral blood mononuclear cells and lymphatic organs compared to the wild-type virus; none of the mutants reverted to the wild type. The neutralizing antibody titers and MV-specific T-cell responses were equivalent in monkeys infected with the viral strains tested, documenting strong adaptive immune responses. In contrast, the inflammatory response was better controlled by wild-type MV, as revealed by inhibition of interleukin-6 and tumor necrosis factor alpha transcription. The interferon response was also better controlled by the wild-type virus than by the defective viruses. Since V- and C-defective MVs induce strong adaptive immune responses while spreading less efficiently, they may be developed as vaccines for immunocompromised individuals. Moreover, MV unable to interact with single innate immunity proteins may be developed for preferential replication in tumors with specific contexts of vulnerability.

* Corresponding author. Mailing address: Department of Molecular Medicine, Mayo Clinic and Foundation, Guggenheim 18-42B, 200 First Street SW, Rochester, MN 55905. Phone: (507) 284-0171. Fax: (507) 262-2122. E-mail: cattaneo.roberto{at}mayo.edu

{triangledown} Published ahead of print on 2 April 2008.

Journal of Virology, June 2008, p. 5359-5367, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.00169-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Toth, A. M., Devaux, P., Cattaneo, R., Samuel, C. E. (2009). Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus. J. Virol. 83: 961-968 [Abstract] [Full Text]  
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