Document Detail

Structural variants of IFNα preferentially promote antiviral functions.
MedLine Citation:
PMID:  21757613     Owner:  NLM     Status:  MEDLINE    
IFNα, a cytokine with multiple functions in innate and adaptive immunity and a potent inhibitor of HIV, exerts antiviral activity, in part, by enhancing apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 (APOBEC3) family members. Although IFNα therapy is associated with reduced viral burden, this cytokine also mediates immune dysfunction and toxicities. Through detailed mapping of IFNα receptor binding sites, we generated IFNα hybrids and mutants and determined that structural changes in the C-helix alter the ability of IFN to limit retroviral activity. Selective IFNα constructs differentially block HIV replication and their directional magnitude of inhibition correlates with APOBEC3 levels. Importantly, certain mutants exhibited reduced toxicity as reflected by induced indoleamine 2,3-dioxygenase (IDO), suggesting discreet and shared intracellular signaling pathways. Defining IFN structure and function relative to APOBEC and other antiviral genes may enable design of novel IFN-related molecules preserving beneficial antiviral roles while minimizing negative effects.
Nancy Vázquez; Hana Schmeisser; Michael A Dolan; Joseph Bekisz; Kathryn C Zoon; Sharon M Wahl
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2011-07-14
Journal Detail:
Title:  Blood     Volume:  118     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-02     Completed Date:  2011-11-15     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2567-77     Citation Subset:  AIM; IM    
Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
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MeSH Terms
Calmodulin / physiology
Cytosine Deaminase / biosynthesis*,  genetics
Gene Expression Regulation
HIV-1 / physiology*
Indoleamine-Pyrrole 2,3,-Dioxygenase / biosynthesis*,  genetics
Interferon-alpha / chemistry*,  genetics,  physiology
Macrophages / immunology*,  virology
Models, Molecular
NF-kappa B / physiology
Protein Conformation
Protein Interaction Mapping
Protein Structure, Tertiary
Receptor, Interferon alpha-beta / chemistry,  physiology
Recombinant Fusion Proteins / physiology
Sequence Homology, Amino Acid
Signal Transduction
Structure-Activity Relationship
Virus Replication / physiology*
Reg. No./Substance:
0/Calmodulin; 0/IFNA2 protein, human; 0/IFNA21 protein, human; 0/IFNAR2 protein, human; 0/Indoleamine-Pyrrole 2,3,-Dioxygenase; 0/Interferon-alpha; 0/NF-kappa B; 0/Recombinant Fusion Proteins; 156986-95-7/Receptor, Interferon alpha-beta; EC protein, human; EC Deaminase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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