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Journal of Virology, January 2008, p. 254-267, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01384-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Expression of the E3L Gene of Vaccinia Virus in Transgenic Mice Decreases Host Resistance to Vaccinia Virus and Leishmania major Infections{triangledown}

Elena Domingo-Gil, Eva Pérez-Jiménez,{dagger} Iván Ventoso,{ddagger} José L. Nájera, and Mariano Esteban*

Department of Cellular and Molecular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Ciudad Universitaria Cantoblanco, 28049 Madrid, Spain

Received 26 June 2007/ Accepted 17 October 2007

The E3L gene of vaccinia virus (VACV) encodes the E3 protein that in cultured cells inhibits the activation of interferon (IFN)-induced proteins, double-stranded RNA-dependent protein kinase (PKR), 2'-5'-oligoadenylate synthetase/RNase L (2-5A system) and adenosine deaminase (ADAR-1), thus helping the virus to evade host responses. Here, we have characterized the in vivo E3 functions in a murine inducible cell culture system (E3L-TetOFF) and in transgenic mice (TgE3L). Inducible E3 expression in cultured cells conferred on cells resistance to the antiviral action of IFN against different viruses, while expression of the E3L gene in TgE3L mice triggered enhanced sensitivity of the animals to pathogens. Virus infection monitored in TgE3L mice by different inoculation routes (intraperitoneal and tail scarification) showed that transgenic mice became more susceptible to VACV infection than control mice. TgE3L mice were also more susceptible to Leishmania major infection, leading to an increase in parasitemia compared to control mice. The enhanced sensitivity of TgE3L mice to VACV and L. major infections occurred together with alterations in the host immune system, as revealed by decreased T-cell responses to viral antigens in the spleen and lymph nodes and by differences in the levels of specific innate cell populations. These results demonstrate that expression of the E3L gene in transgenic mice partly reverses the resistance of the host to viral and parasitic infections and that these effects are associated with immune alterations.

* Corresponding author. Mailing address: Department of Cellular and Molecular Biology, Centro Nacional de Biotecnología, CSIC, Ciudad Universitaria Cantoblanco, 28049 Madrid, Spain. Phone: 34-91-585-4553. Fax: 34-91-585-4506. E-mail: mesteban{at}cnb.uam.es

{triangledown} Published ahead of print on 24 October 2007.

{dagger} Present address: Immunobiology Center, Mount Sinai School of Medicine, Box 1630, One Gustave L. Levy Place, New York, NY 10029.

{ddagger} Present address: Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas-Universidad Autónoma, Facultad de Ciencias, Cantoblanco, Universidad Autónoma de Madrid, 28049 Madrid, Spain.

Journal of Virology, January 2008, p. 254-267, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01384-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Myskiw, C., Arsenio, J., van Bruggen, R., Deschambault, Y., Cao, J. (2009). Vaccinia Virus E3 Suppresses Expression of Diverse Cytokines through Inhibition of the PKR, NF-{kappa}B, and IRF3 Pathways. J. Virol. 83: 6757-6768 [Abstract] [Full Text]  


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