A Family of Novel Cyclophilins, Conserved in the Mimivirus Genus of the Giant DNA Viruses

The cyclophilin (abbreviated here as CYN) family represents a large group of protein prolyl isomerase (PPIase), many of which are also chaperones that promote proper folding of a large variety of client proteins. Over the past few years, megaviruses with giant DNA genomes were discovered and placed in the order Megavirales. Recently, the first complete genome sequence of Acanthamoebaae polyphaga mimivirus, a member of the Mimiviridae family of the Megavirales order, revealed a novel CYN that lacked PPIase activity and contained unique peptide insertions. To examine the universality of this unique CYN, I have reviewed and compared all CYN sequences found in the Megavirales genomes that are currently available. The results showed that multiple unique sequence features are indeed highly conserved in CYNs of all members of the Mimivirus genus, whereas viruses of the other genera of this family encode canonical CYNs only. Overall, the primary structures of all Mimivirus CYNs were highly similar, but different from those in the other genera, although the higher order structures were conserved across genera. In summary, this review establishes a family of novel but conserved cyclophilins that occur in a single viral genus.