Document Detail

Interferon-inducible transmembrane protein 3 (IFITM3) restricts reovirus cell entry.
MedLine Citation:
PMID:  23649619     Owner:  NLM     Status:  MEDLINE    
Reoviruses are double-stranded RNA viruses that infect the mammalian respiratory and gastrointestinal tract. Reovirus infection elicits production of type I interferons (IFNs), which trigger antiviral pathways through the induction of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified, the functions of many of these genes are unknown. The interferon-inducible transmembrane (IFITM) proteins are one class of ISGs that restrict the cell entry of some enveloped viruses, including influenza A virus. One family member, IFITM3, localizes to late endosomes, where reoviruses undergo proteolytic disassembly; therefore, we sought to determine whether IFITM3 also restricts reovirus entry. IFITM3-expressing cell lines were less susceptible to infection by reovirus, as they exhibited significantly lower percentages of infected cells in comparison to control cells. Reovirus replication was also significantly reduced in IFITM3-expressing cells. Additionally, cells expressing an shRNA targeting IFITM3 exhibited a smaller decrease in infection after IFN treatment than the control cells, indicating that endogenous IFITM3 restricts reovirus infection. However, IFITM3 did not restrict entry of reovirus infectious subvirion particles (ISVPs), which do not require endosomal proteolysis, indicating that restriction occurs in the endocytic pathway. Proteolysis of outer capsid protein μ1 was delayed in IFITM3-expressing cells in comparison to control cells, suggesting that IFITM3 modulates the function of late endosomal compartments either by reducing the activity of endosomal proteases or delaying the proteolytic processing of virions. These data provide the first evidence that IFITM3 restricts infection by a nonenveloped virus and suggest that IFITM3 targets an increasing number of viruses through a shared requirement for endosomes during cell entry.
Amanda A Anafu; Christopher H Bowen; Christopher R Chin; Abraham L Brass; Geoffrey H Holm
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-05-06
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  288     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-17     Completed Date:  2013-08-21     Revised Date:  2014-06-17    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17261-71     Citation Subset:  IM    
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MeSH Terms
Capsid / metabolism
Endosomes / virology
Gene Expression
Gene Knockdown Techniques
HeLa Cells
Host-Pathogen Interactions
Interferon-alpha / physiology
Mammalian orthoreovirus 3 / physiology*
Membrane Proteins / physiology*
Orthoreovirus, Mammalian / physiology
RNA, Small Interfering / genetics
RNA-Binding Proteins / physiology*
Virion / physiology
Virus Assembly
Virus Internalization*
Virus Replication
Grant Support
Reg. No./Substance:
0/IFITM3 protein, human; 0/Interferon-alpha; 0/Membrane Proteins; 0/RNA, Small Interfering; 0/RNA-Binding Proteins

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