A Severe Acute Respiratory Syndrome Coronavirus That Lacks the E Gene is Attenuated in Vitro and in Vivo.
From: Department of Molecular and Cell Biology, Centro Nacional de Biotecnología, CSIC, Darwin 3, Campus Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain.
Journal of virology
- Publish Date: Feb 2007
- ISSN: 0022-538X
- Volume: 81
- Issue: 4
- Pages: 1701-13
- Medium: Print
- Language: English
- Citation (JAMA): DeDiego Marta L, Alvarez Enrique, Almazán Fernando, et al. A Severe Acute Respiratory Syndrome Coronavirus That Lacks the E Gene is Attenuated in Vitro and in Vivo.. J. Virol. Feb 2007;81:1701-13
Abstract
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-DeltaE) 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-DeltaE 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-DeltaE 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.
Mesh Headings (Keywords): Animals, Caco-2 Cells, Cercopithecus aethiops, Cricetinae, Gene Deletion, Humans, Respiratory System, SARS Virus, Severe Acute Respiratory Syndrome, Vero Cells, Viral Structural Proteins, Virus Replication
Check for Full Text / PubMed Unique Identifier (PMID): 17108030
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