LRRFIP1 can recognize both AT-rich B-form dsDNA and GC-rich Z-form dsDNA (Yang P et al. 2010). Induction of IFN-beta by LRRFIP1 was enhanced with the presence of hepatitis C virus (Liu Y et al. 2015). Overexpression of LRRFIP1 in hepatocyte derived cellular carcinoma cell lines (Huh7 and Huh7.5.1) inhibited HCV replication. However, HCV infection did not regulate intracellular expression of LRRFIP1 (Liu Y et al. 2015). In addition, the C-terminus of LRRFIP1 has been described as having nucleic acid-binding activity, including the transactivating response region (TAR) hairpin of HIV (Liu YT & Yin HL 1998; Choe N et al. 2013). Moreover, LRRFIP1 induced type I IFNs in 3T3 cells in the presence of influenza virus and contributed to the production of IFN-beta in mouse macrophages induced by VSV (vesicular stomatitis virus) and Listeria monocytogenes (Bagashev A et al. 2010; Yang P et al. 2010).

LRRFIP1 contains three domains, an N-terminal helical region of unknown function, a central coiled coil (CC) domain that interacts with protein flightless I homolog (FLII), and a C-terminal DNA binding or nucleic acid recognition domain (DBD). The structural and biophysical studies revealed that the CC-domain of LRRFIP1 forms stable homodimer in solution while the CC-DBD construct was found to be an oligomer suggesting that the full length LRRFIP1 may also form dimers or larger oligomers upon DNA binding (Nguyen JB and Modis Y 2012).