EndoU is a novel regulator of AICD during peripheral B cell selection

Poe, Jonathan C.; Kountikov, Evgueni I.; Lykken, Jacquelyn M.; Natarajan, Abirami; Marchuk, Douglas A.; Tedder, Thomas F.

Viral orthologs of EndoU also exist ( Fig. 8 B) . Nsp15 (NendoU) is unique to the nidovirus family of ssRNA viruses, which includes the SARS coronavirus (Laneve et al., 2003; Bhardwaj et al., 2004; Ivanov et al., 2004; Gioia et al., 2005) . Although Nsp15 is required for viral replication, specific Nsp15 substrates have not been identified and, surprisingly, appear to exclude the viral genome itself (Ivanov et al., 2004) . Nsp15 has been postulated to suppress host immune responses (Ricagno et al., 2006) and to facilitate apoptosis in cells expressing the MAVS (mitochondrial anti-viral signaling) adapter protein that induces host anti-viral responses (Lei et al., 2009) . Mouse hepatitis virus is also a member of the nidovirus family, is lymphotropic, and induces immunosuppression at least in part through the elimination of developing B cells (Lamontagne et al., 1989; Jolicoeur and Lamontagne, 1994) . It therefore remains possible that mouse EndoU and hepatitis virus Nsp15 may target similar ssRNA substrates in B cells despite their evolutionary divergence. If true, each would have the capacity to suppress immune responses by inducing B cell AICD.