The geographical distribution of
schizophrenia was previously shown to correlate with the global distribution of tick-borne flaviviruses. The correlation suggests a natural resistance gene to flaviviruses could be involved in
schizophrenia. The flavivirus resistance gene, Flv, a gene found in wild mice and certain in-bred strains, confers resistance to flaviviruses through the interaction of cellular
proteins with the flaviviral
3' untranslated regions (
UTRs). Although the sequence and product of Flv are unknown, translation
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 that inhibit
RNA growth. A study was performed to assess the homology between flaviviral
UTRs, subunits of
EF-1, and selected
proteins reported as abnormal in
schizophrenia. The
UTRs of four flaviviruses with wide geographical and phylogenic distribution were manually translated. Using the National Biomedical Research Foundation
protein databank, the amino acid sequences were correlated with the amino acid sequences of selected
proteins. The amino acid sequences of the
EF-1 subunits were then correlated with the same
proteins. Similar
amino acid correlations between the
proteins,
EF-1 subunits and viral
UTRs suggest that translational pathophysiology resulting from the product of Flv can be postulated as the cause of
protein abnormalities observed in
schizophrenia.