Novel plant-derived recombinant human interferons with broad spectrum antiviral activity

► Hybrid, human interferons expressed in plants by gene crossbreeding. ► Hybrid interferons identified with improved antiviral properties. ► Several hybrid interferons inhibit interferon resistant viruses. ► Structural analysis suggests improved activity is related to receptor binding. Type I interf...

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Bibliographic Details
Published in:	Antiviral research Vol. 92; no. 3; pp. 461 - 469
Main Authors:	Koehler, Jeffrey W., Dupuy, Lesley C., Garrison, Aura R., Beitzel, Brett F., Richards, Michelle J., Ripoll, Daniel R., Wallqvist, Anders, Teh, Shia-Yen, Vaewhongs, Andrew A., Vojdani, Fakhrieh S., Padgett, Hal S., Schmaljohn, Connie S.
Format:	Journal Article
Language:	English
Published:	Kidlington Elsevier B.V 01-12-2011 Elsevier
Subjects:	Amino Acid Sequence Amino acids Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral activity Antiviral agents Antiviral Agents - pharmacology Biological and medical sciences Chlorocebus aethiops Ebola virus Humans Immune response Infection Interferon Interferon Type I - chemistry Interferon Type I - genetics Interferon Type I - pharmacology Medical sciences Microbial Sensitivity Tests Models, Molecular Molecular Sequence Data Monkeypox virus Nicotiana - genetics Pharmacology. Drug treatments Plants Protein Conformation Recombinant Proteins - chemistry Recombinant Proteins - genetics Recombinant Proteins - pharmacology Rift Valley fever virus Sequence Alignment Type I interferons Venezuelan equine encephalitis virus Vero Cells Viruses - drug effects IFNs Rift Valley fever virus Type I interferons EBOV MPXV PSPP Venezuelan equine encephalitis virus IFNAR VEEV PDB GFP Ebola virus BSA RVFV Monkeypox virus GRAMMR Venezuelan equine encephalomyelitis virus Togaviridae Rift valley fever virus Plant Bunyaviridae Gene Filoviridae Genetics Antiviral Filovirus Activity spectrum Phlebovirus Human Chordopoxvirinae Nucleotide sequence Orthopoxvirus Sandfly fever group virus Cytokine Biological activity Virus Mononegavirales Poxviridae Alphavirus Interferon Veterinary
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Summary:	► Hybrid, human interferons expressed in plants by gene crossbreeding. ► Hybrid interferons identified with improved antiviral properties. ► Several hybrid interferons inhibit interferon resistant viruses. ► Structural analysis suggests improved activity is related to receptor binding. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0166-3542 1872-9096
DOI:	10.1016/j.antiviral.2011.10.008