C. LANZ¹, E.E. MÜLLER¹, S. STERTZ<sup>1

1</sup>Institute of Medical Virology, University of Zurich, Zurich, Switzerland

Interferon-inducible transmembrane proteins (IFITMs) have been identified as potent antiviral factors inhibiting entry of a whole variety of viruses, including influenza A virus (IAV). Recently is has been described that in addition to blockage of fusion of viral and host cell membranes in target cells IFITMs are also incorporated into budding HIV virions. IFITM incorporation has been associated with a decreased fusion capacity of virions. Furthermore, IFITMs have been shown to interact with HIV envelope glycoproteins in virus producer cells, resulting in decreased envelope processing and incorporation into virions.
Here, we describe studies on IFITM incorporation into IAV particles and its consequences on virus infectivity. We assessed the effect of IFITM incorporation on the envelope-mediated fusion process by comparing the entry efficiency of HIV virus-like particles (VLPs) pseudotyped with envelope proteins of IAV, HIV or VSV in the presence or absence of IFITM3. We observed that all virions tested incorporated IFITM3, which led to a reduction in entry efficiency. To detect potential effects specific to IAV, IFITM incorporation and its consequences were also studied in an IAV-based VLP system. Our results suggest that also in the IAV-based system the presence of IFITM3 in the producer cells leads to reduced entry efficiency at or before the fusion step. Ongoing studies aim to test whether the results obtained in the VLP system can be extrapolated to wildtype virus.