Abstract

The ability of bats to act as virus reservoirs and seemingly tolerate viral infections that are highly pathogenic in other species has cast a spotlight onto bat immunology and prompted the question ‘are bats special?

Host interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral restriction factors which block virus entry into cells. Of these, IFITM3 potently inhibits a diverse range of viruses that enter cells through acidic endosomes. In humans, single nucleotide polymorphisms in IFITM3 have been associated with increased virus-induced morbidity. However, the function of IFIT Ms in bats, the natural hosts of many of the zoonotic and emerging viruses restricted by human IFITM3 , was previously unknown. In this talk I will discuss my comparative evolution-guided research on bat IFIT Ms. The adaptive evolution we identified for bat IFIT Ms suggests that they serve an antiviral role in vivo, and that at least some bat viruses must have exerted major fitness costs on their hosts. Microbat IFITM3 is an endosomal restriction factor capable of restricting the cell entry of lyssaviruses, flaviviruses, alphaviruses, and influenza A virus. We found that a naturally-polymorphic site within the conserved CD225 domain affects the antiviral activity and S-palmitoylation of microbat IFITM3 . Furthermore, S-palmitoylation, a lipid post-translational modification, is crucial for antiviral restriction and proper subcellular localisation of microbat IFITM3 .

Ultimately, illuminating the molecular basis of IFITM restriction and of the intimate association between bats and their viruses can better arm us to combat the emergence and impact of bat-borne viruses.