Interestingly, targeting the E3 ligase activity of TRIM5 to sites of tick-borne flavivirus replication through fusion with CypA is not sufficient to restrict infection, despite a clear requirement for CypA in flavivirus replication (Chiramel et al., 2016; Qing et al., 2009; Vidotto et al., 2017), perhaps because CypA binds to different NS proteins (NS5, NS4A) (Qing et al., 2009; Vidotto et al., 2017) than does TRIM5α. The gene discussed is RAF1; the disease is infection.