IFITM3: Variant in Cell Defense Protein Can Leave You Vulnerable to Flu

Cells of the human body defend themselves against viral infection, but faults in this system could make some people susceptible to suffering particularly bad flu. IFITM3 (interferon-induced transmembrane protein 3) is an antiviral protein that has recently appeared in the news because a defective variant has been associated with an increased risk of severe influenza, with particular significance within the Chinese population.

Zhang et al. analyzed the occurrence and effect of the SNP (single nucleotide polymorphism) rs12252-C in Chinese patients with influenza A virus infection during the 2009 H1N1 flu pandemic. This SNP, which causes a truncation of the IFITM3 protein, had previously been linked to influenza disease severity in Northern Europeans, but in that population the susceptibility allele is rare. In contrast, a quarter of Han Chinese people are homozygous for this allele. In their study, the researchers discovered that over two thirds of patients with severe influenza had two copies of this ‘C’ allele, whereas in patients with mild flu, the proportion with the CC genotype was almost the identical to the general Han Chinese population. It was estimated that CC individuals are six times more likely to suffer from severe rather than mild flu than those heterozygous or homozygous for the normal IFITM3 allele.

Immunohistochemistry-paraffin: IFITM3 antibody

These findings are important in a number of ways. For instance, determining the genotype at the rs12252 SNP of IFITM3 could be used to identify individuals most at risk of severe flu, and so tailor medical treatment, both in the healthy population (targeting vaccines to those most at risk) and those already infected with the flu virus (adapting their treatment to take this susceptibility into account). Consideration of this SNP would also be of benefit in future studies of the influenza virus, including clinical trials. It will be interesting to see how this variant of IFITM3 affects disease severity in other populations and with other viruses.