A novel mechanism to explain protein abnormalities in schizophrenia based on the flavivirus resistance gene

The geographical distribution of schizophrenia was previously shown to corr elate with the global distribution of tick-borne flaviviruses. The correlat ion suggests a natural resistance gene to flaviviruses could be involved in schizophrenia. The flavivirus resistance gene, Flv, a gene found in wild m ice and certain in-bred strains, confers resistance to flaviviruses through the interaction of cellular proteins with the flaviviral 3' untranslated r egions (UTRs). Although the sequence and product of Flv are unknown, transl ation elongation factor alpha -1 (EF-1) is a protein known to interact with the 3' UTR flavivirus RNA, forming some complexes with long half-lives tha t inhibit RNA growth. A study was performed to assess the homology between flaviviral UTRs, subunits of EF-1, and selected proteins reported as abnorm al in schizophrenia. The UTRs of four flaviviruses with wide geographical a nd phylogenic distribution were manually translated. Using the National Bio medical Research Foundation protein databank, the amino acid sequences were correlated with the amino acid sequences of selected proteins. The amino a cid sequences of the EF-1 subunits were then correlated with the same prote ins. Similar amino acid correlations between the proteins, EF-1 subunits an d viral UTRs suggest that translational pathophysiology resulting from the product of Flv can be postulated as the cause of protein abnormalities obse rved in schizophrenia.