Defining the range of pathogens susceptible to ifitm3 restriction using a knockout mouse model

Everitt, Aaron R., Clare, Simon, McDonald, Jacqueline U., Kane, Leanne, Harcourt, Katherine, Ahras, Malika, Lall, Amar, Hale, Christine, Rodgers, Angela, Young, Douglas B., Haque, Ashraful, Billker, Oliver, Tregoning, John S., Dougan, Gordon and Kellam, Paul (2013) Defining the range of pathogens susceptible to ifitm3 restriction using a knockout mouse model. PLoS ONE, 8 11: . doi:10.1371/journal.pone.0080723


Author Everitt, Aaron R.
Clare, Simon
McDonald, Jacqueline U.
Kane, Leanne
Harcourt, Katherine
Ahras, Malika
Lall, Amar
Hale, Christine
Rodgers, Angela
Young, Douglas B.
Haque, Ashraful
Billker, Oliver
Tregoning, John S.
Dougan, Gordon
Kellam, Paul
Title Defining the range of pathogens susceptible to ifitm3 restriction using a knockout mouse model
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-11-21
Sub-type Article (original research)
DOI 10.1371/journal.pone.0080723
Open Access Status DOI
Volume 8
Issue 11
Total pages 12
Place of publication San Francisco, United States
Publisher Public Library of Science
Language eng
Abstract The interferon-inducible transmembrane (IFITM) family of proteins has been shown to restrict a broad range of viruses in vitro and in vivo by halting progress through the late endosomal pathway. Further, single nucleotide polymorphisms (SNPs) in its sequence have been linked with risk of developing severe influenza virus infections in humans. The number of viruses restricted by this host protein has continued to grow since it was first demonstrated as playing an antiviral role; all of which enter cells via the endosomal pathway. We therefore sought to test the limits of antimicrobial restriction by Ifitm3 using a knockout mouse model. We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium , Mycobacterium tuberculosis) or protozoan (Plasmodium berghei ) pathogens, despite in vitro evidence. However, Ifitm3 is capable of restricting respiratory syncytial virus (RSV) in vivo either through directly restricting RSV cell infection, or by exerting a previously uncharacterised function controlling disease pathogenesis. This represents the first demonstration of a virus that enters directly through the plasma membrane, without the need for the endosomal pathway, being restricted by the IFITM family; therefore further defining the role of these antiviral proteins.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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