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Journal of Virology, February 2007, p. 1701-1713, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.01467-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Severe Acute Respiratory Syndrome Coronavirus That Lacks the E Gene Is Attenuated In Vitro and In Vivo{triangledown}

Marta L. DeDiego,1 Enrique Álvarez,1 Fernando Almazán,1 María Teresa Rejas,2 Elaine Lamirande,3 Anjeanette Roberts,3 Wun-Ju Shieh,4 Sherif R. Zaki,4 Kanta Subbarao,3 and Luis Enjuanes1*

Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CSIC), Campus Universidad Autónoma, Darwin 3, Cantoblanco, 28049 Madrid, Spain,1 Centro de Biología Molecular (CSIC-UAM), Facultad de Ciencias, Campus Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain,2 Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,3 Infectious Disease Pathology Activity, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 303334

Received 11 July 2006/ Accepted 8 November 2006

A deletion mutant of severe acute respiratory syndrome coronavirus (SARS-CoV) has been engineered by deleting the structural E gene in an infectious cDNA clone that was constructed as a bacterial artificial chromosome (BAC). The recombinant virus lacking the E gene (rSARS-CoV-{Delta}E) was rescued in Vero E6 cells. The recovered deletion mutant grew in Vero E6, Huh-7, and CaCo-2 cells to titers 20-, 200-, and 200-fold lower than the recombinant wild-type virus, respectively, indicating that although the E protein has an effect on growth, it is not essential for virus replication. No differences in virion stability under a wide range of pH and temperature were detected between the deletion mutant and recombinant wild-type viruses. Although both viruses showed the same morphology by electron microscopy, the process of morphogenesis seemed to be less efficient with the defective virus than with the recombinant wild-type one. The rSARS-CoV-{Delta}E virus replicated to titers 100- to 1,000-fold lower than the recombinant wild-type virus in the upper and lower respiratory tract of hamsters, and the lower viral load was accompanied by less inflammation in the lungs of hamsters infected with rSARS-CoV-{Delta}E virus than with the recombinant wild-type virus. Therefore, the SARS-CoV that lacks the E gene is attenuated in hamsters, might be a safer research tool, and may be a good candidate for the development of a live attenuated SARS-CoV vaccine.

* Corresponding author. Mailing address: Department of Molecular and Cell Biology, Centro Nacional de Biotecnología, CSIC, Darwin 3, Campus Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain. Phone: 34 91 585 4555. Fax: 34 91 585 4915. E-mail: L.Enjuanes{at}cnb.uam.es.

{triangledown} Published ahead of print on 15 November 2006.

Journal of Virology, February 2007, p. 1701-1713, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.01467-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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