Among the most potent members of the sensitizer class were the previously described proviral host factor IFITM3 and its homolog IFITM1 ( Table 7 in Supporting Information S1). IFITM3 has been reported to be required for restriction of viral infection and is thought to inhibit viral entry [4, 14] . These gene products are interferon responsive, and depletion was associated with enhanced viral pathogenicity and enhanced viral protein production at limiting MOIs (1 and 0.1) as compared to controls (Figure 2A , B, C). Unexpectedly, cells depleted of IFITM3 produced fewer infection competent viral particles as determined by secondary infection of MDCK cells with cell culture supernatants (Figure 2 A, E). For these assays, HBEC30 cell cultures were infected with an MOI of 5 for 48 hours post transfection with siRNA pools. Supernatants were collected 24 hours post infection and used to infect confluent MDCK cell cultures. Notably, we observed enhanced frequency as well as enhanced amplitude of viral protein accumulation in IFITM3 depleted cells during primary infection. Reduced production of infectious particles, in the face of enhance viral protein production, may therefore be a consequence of either limiting host factors or disruption of viral protein/host factor stoichiometry required for assembly of viable viral particles. Of interest, the viral cytophathic effect was greatly enhanced upon IFITM3 depletion in the presence or absence of the virulence factor NS1, a viral protein known to block many of the innate immunity responses [15] [16] [17] [18] [19] (figure 2F, G). However, deletion of NS1 results in complete failure of infectious particle production even upon IFITM3 depletion ( Figure 2H ). These observations would place IFITM3 function early in the viral life cycle and independent of NS1 function, consistent with reports that indicate IFITM3's antiviral activity is at the level of viral entry [14] .