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Accession Number ADA571135
Title Novel Plant-Derived Recombinant Human Interferons with Broad Spectrum Antiviral Activity.
Publication Date Oct 2011
Media Count 10p
Personal Author A. R. Garrison B. F. Beitzel J. W. Koehler L. C. Dupuy M. J. Richards
Abstract Type I interferons (IFNs) are potent mediators of the innate immune response to viral infection. IFNs released from infected cells bind to a receptor (IFNAR) on neighboring cells, triggering signaling cascades that limit further infection. Subtle variations in amino acids can alter IFNAR binding and signaling outcomes. We used a new gene crossbreeding method to generate hybrid, type I human IFNs with enhanced antiviral activity against four dissimilar, highly pathogenic viruses. Approximately 1400 novel IFN genes were expressed in plants, and the resultant IFN proteins were screened for antiviral activity. Comparing the gene sequences of a final set of 12 potent IFNs to those of parent genes revealed strong selection pressures at numerous amino acids. Using three-dimensional models based on a recently solved experimental structure of IFN bound to IFNAR, we show that many but not all of the amino acids that were highly selected for are predicted to improve receptor binding.
Keywords Amino acids
Antiviral agents
Assaying
Cells(Biology)
Ebola virus
Gene expression
Ifn(Interferon)
Interferon
Monkeypox virus
Plant-derived recombinant human interferons
Proteins
Receptor sites(Physiology)
Rift valley fever virus
Type i interferons
Venezuelan equine encephalitis virus
Venezuelan equine encephalomyelitis

 
Source Agency Non Paid ADAS
NTIS Subject Category 57Q - Pharmacology & Pharmacological Chemistry
Corporate Author Army Medical Research Inst. of Infectious Diseases, Fort Detrick, MD. Virology Div.
Document Type Journal article
Title Note Journal article.
NTIS Issue Number 1315
Contract Number N/A

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