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Product Name:
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Recombinant Infectious Mouse-Adapted Mutant of Urbani Strain with Non-Functional Exoribonuclease (icSARS-CoV-MA15-ExoN1)
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Manufacturer:
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BEI Resources
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Taxonomy:
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Virus Classification: Coronaviridae, Coronavirinae, Betacoronavirus
Agent: SARS coronavirus (SARS-CoV)
Strain/Isolate: Recombinant infectious mouse-adapted mutant of Urbani strain with non-functional exoribonuclease (icSARS-CoV-MA15-ExoN1)1
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Additional Information:
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NR-44008 is an engineered recombinant coronavirus based on a full-length infectious clone of the SARS-CoV, Urbani genome. SARS-CoV, Urbani was serially passaged in the lungs of BALB/c mice fifteen times, and a biological clone, MA15, was recovered which was 100% lethal in BALB/c mice within six days of inoculation.1 Six coding mutations associated with mouse adaptation and increased virulence were identified and inserted into cDNA clones that were used to construct and rescue an infectious recombinant mutant clone of SARS-CoV, Urbani, as previously descibed.2 The recombinant virus was highly virulent and lethal, reproducing the phenotype of the biologically derived MA15.1 Alanine substitution mutations in the DEDD motif 1 of nonstructural protein 14 (nsp14) that inactivate the coronavirus 3’→5’ exoribonuclease (ExoN) were subsequently engineered onto the MA15 background.3 The resulting virus, termed MA-ExoN (or MA15 ExoN1), expresses a stable mutator phenotype with profoundly decreased fidelity and attenuation of pathogenesis both in young and in aged immunosenescent mice.4 The ExoN inactivation genotype and mutator phenotype did not revert to virulence even after serial passage or long-term persistent infection in vivo. Vaccination with the live attenuated virus protected aged mice from lethal challenge with “wild type” mouse adapted SARS-CoV.
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Material Provided:
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Each vial contains approximately 1 mL of cell lysate and supernatant from Vero E6 (C1008) cells (ATCC® CRL-1586™) infected with icSARS-CoV-MA15-ExoN1.
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Packing/Storage:
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NR-44008 was packaged aseptically in cryovials. The product is provided frozen and should be stored at -60°C or colder immediately upon arrival. For long-term storage, the vapor phase of a liquid nitrogen freezer is recommended. Freeze-thaw cycles should be avoided.
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Disclaimers:
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You are authorized to use this product for research use only. It is not intended for human use. Use of this product is subject to the terms and conditions of the BEI Resources Material Transfer Agreement (MTA). The MTA is available on our Web site at www.beiresources.org. While BEI Resources uses reasonable efforts to include accurate and up-to-date information on this product sheet, neither ATCC® nor the U.S. Government makes any warranties or representations as to its accuracy. Citations from scientific literature and patents are provided for informational purposes only. Neither ATCC® nor the U.S. Government warrants that such information has been confirmed to be accurate. This product is sent with the condition that you are responsible for its safe storage, handling, use and disposal. ATCC® and the U.S. Government are not liable for any damages or injuries arising from receipt and/ or use of this product. While reasonable effort is made to ensure authenticity and reliability of materials on deposit, the U.S. Government, ATCC®, their suppliers and contributors to BEI Resources are not liable for damages arising from the misidentification or misrepresentation of products. |
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Patents or other restrictions:
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NR-44008 is claimed in U.S. Patent Number 7,618,802 and the continuations, continuations-in-part, re-issues and foreign counterparts thereof. Commercial use may require a license from the University of North Carolina at Chapel Hill. For further information contact the Office of Technology Development, Campus Box 4105, 308 Bynum Hall, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, 27599-4105, (919) 966-3929.
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References:
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1. Roberts, A., et al. “A Mouse-Adapted SARS-Coronavirus Causes Lethality and Mortality in BALB/c Mice.” PLoS Pathog. 3 (2007): e5. PubMed: 17222058.
2. Yount, B., et al. “Severe Acute Respiratory Syndrome Coronavirus Group-Specific Open Reading Frames Encode Nonessential Functions for Replication in Cell Cultures and Mice.” J. Virol. 79 (2005): 14909-14922. PubMed: 16282490.
3. Eckerle, L. D., et al. “Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication is Revealed by Complete Genome Sequencing.” PLoS Pathog. 6 (2010): e1000896. PubMed: 20463816.
4. Graham, R. L., et al. “A Live, Impaired Fidelity Coronavirus Vaccine Protects in an Aged, Immunocompromised Mouse Model of Lethal Disease.” Nat Med. 18 (2012): 1820-1826. PubMed: 23142821.
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Citation:
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Acknowledgment for publications should read "The following reagent was obtained through BEI Resources, NIAID, NIH: SARS Coronavirus, Recombinant Infectious Mouse-Adapted Mutant of Urbani Strain with Non-Functional Exoribonuclease (icSARS-CoV-MA15-ExoN1), NR-44008."
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Biosafety Level:
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3
Appropriate safety procedures should always be used with this material. Laboratory safety is discussed in the following publication: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, and National Institutes of Health. Biosafety in Microbiological and Biomedical Laboratories (BMBL). Current Edition. Washington, DC: U.S. Government Printing Office.
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