Defining the range of pathogens susceptible to Ifitm3 restriction using a knockout mouse model

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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
Animals
Bacteria/*metabolism
Citrobacter rodentium/growth & development/physiology
Homeostasis
Kinetics
Malaria/parasitology
Membrane Proteins/deficiency/*metabolism
Mice
Inbred C57BL
Mice
Knockout
Models
Animal
Mycobacterium tuberculosis/growth & development/physiology
Phenotype
Plasmodium berghei/growth & development/*physiology
Respiratory Syncytial Viruses/growth & development/*physiology
Salmonella typhimurium/physiology

By the author/editor: Everitt, Aaron R; Clare, Simon; McDonald, Jacque ...; Kane, Leanne; Harcourt, Kather ...; Ahras, Malika; show more...; Lall, Amar; Hale, Christine; Rodgers, Angela; Young, Douglas B; Haque, Ashraful; Billker, Oliver; Tregoning, John ...; Dougan, Gordon; Kellam, Paul; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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