Interferon-induced transmembrane proteins (IFITMs) are well-known to restrict numerous viral pathogens. A new study of CRC 1279 members shows that the opposite is the case for SARS-CoV-2, the coronavirus responsible for the current COVID-19 pandemic.

According to the manuscript, recently accepted by „Nature Communications“, endogenous IFITMs unexpectedly promote SARS-CoV-2. „Our results show that SARS-CoV-2 hijacks human IFITM proteins for efficient infection“,  the shared first authors Caterina Prelli Bozzo and Rayhane Nchioua, PhD students at the Institute of Molecular Virology, agree on.

This stands in contrast to data from other groups, suggesting that IFITM proteins inhibit human coronaviruses including SARS-CoV-2. „Previous results were obtained using artificial conditions in cell lines overexpressing IFITMs“, explains Frank Kirchhoff, senior author of the study. “We could verify these data using such artificial settings”. More importantly, however, the team around Sparrer, Kirchhoff and other CRC 1279 members moved to more physiologically relevant systems for SARS-CoV-2 analyzing effects of endogenously expressed IFITMs in primary human lung cells. „We show that IFITMs are required for efficient SARS-CoV-2 infection under physiological conditions“, says Sparrer.

Using advanced microscopy analyses and interaction assays, the team showed that the Spike protein, which is required for virus entry into human cells interacts with IFITMs, promoting subsequent virus entry. If the researchers, on the other hand, depleted IFITMs in human cells, the infection was inefficient and the cells only produced very small amounts of infectious SARS-CoV-2.  

The unexpected finding that IFITM proteins serve as cofactors for SARS-CoV-2-infection may even help to develop novel therapeutics against COVID-19. In support of this, the team showed that antibodies, blocking IFITMs and IFITM-derived peptides inhibit infection of human lung, heart and gut cells, the primary targets for virus transmission and dissemination in the human body. The finding that SARS-CoV-2 hijacks factors that usually have antiviral activity helps to explain why this virus is so efficient in spreading and evading our immune system.