ABSTRACT
IFITM3 restricts cellular infection by multiple important viral pathogens, and is particularly critical for the innate immune response against influenza virus. Expression of IFITM3 expands acidic endolysosomal compartments and prevents fusion of endocytosed viruses, leading to their degradation. This small, 133 amino acid, antiviral protein is controlled by at least four distinct post-translational modifications. Positive regulation of IFITM3 antiviral activity is provided by S-palmitoylation, while negative regulatory mechanisms include lysine ubiquitination, lysine methylation and tyrosine phosphorylation. Herein, we describe specific insights into IFITM3 trafficking and activity that were provided by studies of IFITM3 post-translational modifications, and discuss evidence suggesting that IFITM3 adopts multiple membrane topologies involving at least one intramembrane domain in its antivirally active conformation.
Financial & competing interests disclosure
Research in the Yount laboratory is supported by the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) (grant R00AI095348) and the Ohio State University Public Health Preparedness for Infectious Diseases program. NM Chesarino is supported by the Ohio State University Systems and Integrative Biology Training Program (NIH/NIGMS grant T32GM068412) and TM McMichael is supported by the American Society for Microbiology Robert D. Watkins Graduate Research Fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.