ATS 2009 · San Diego
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| Abstract Number: 4250 |
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| Contact/Presenting Author: Christine L. Wohlford-Lenane | |
| Department/Institution: University of Iowa | |
| Address: 500 Newton Rd, 240 EMRB | |
| City/State/Zip/Country: Iowa City, IA, 52242 | |
| Phone: 319-335-6933 Fax: E-mail: c-wohlford-lenane@uiowa.edu | |
| ATS member: No Student or in training: No | |
| Funding Source: NIH. | |
Abstract Category: 10.15 - Treatment of Respiratory Infections |
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| Presentation format: Poster Only | |
| Preview Disclosure | |
| Travel Award: No | |
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Publication of email address:
Yes, c-wohlford-lenane@uiowa.edu I confirm that all authors listed on this abstract have knowledge of the abstract submission: Yes |
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Title: Protective Role of Griffithsin in Severe Acute Respiratory Syndrome Pulmonary Infection C. L. Wohlford-Lenane1, B. Giomarelli2, J. B. McMahon2, B. R. O'Keefe2, D. Meyerholz3 and P. B. McCray1. 1University of Iowa, Iowa City, IA; 2National Cancer Institute, Frederick, MD and 3Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA. Rationale: Severe Acute Respiratory Syndrome (SARS) became a threat to worldwide health in 2002, with over 8000 diagnosed cases reported, causing approximately 800 deaths. While much has been discovered of the coronavirus that causes SARS, little headway has been made toward therapeutic approaches to prevent infection or halt progression. In this study, we evaluated the antiviral effects of the algae protein, Griffithsin (GRFT) as a therapeutic candidate for SARS-CoV infection prevention. Methods: Mice were intranasally inoculated with mouse adapted ( MA15) Urbani SARS-CoV (3.0 x 105 pfu), treated with GRFT or sham, weighed daily and euthanized on days 2, 4 and 10 post infection. Lungs were excised and used for viral titering, histopathological analysis, and cytokine and chemokine analysis. Results: Untreated mice inoculated with SARS-CoV had a 30% survival rate and those that survived had a 35% reduction in weight. Mice treated with GRFT and inoculated with SARS-CoV had a 100% survival rate with no reduction in weight. Antiviral activity of GRFT was analyzed by titering SARS-CoV in homogenized lung supernatant. This showed a 20-fold decrease in pfu/ml at in mice treated with GRFT compared to those that received no treatment. Lungs from SARS-CoV only group had early necrotizing bronchiolitis followed by predominent edema. GRFT treated lungs had significant perivascular infiltrates from d2-10 but less severe scores for edema and necrotizing bronchiolitis. We are currently investigating various cytokine and chemokine protein levels in lung homogenates. Conclusions: These results identify GRFT as a potent inhibitor of SARS-CoV infection and disease progression in mice. GRFT may be beneficial in the prophylaxis or treatment of SARS coronavirus infection. |
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