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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

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

Publication and Content Type

ref (subject category)

art (subject category)