Factor involved in latent infection with herpesvirus, and use thereof

Abstract

Disclosed are a protein and a gene each of which is a factor involved in latent infection with a herpesvirus. An antibody against the factor was detected in approximately 50% of patients suffering from mental disorders, whereas the antibody was hardly detected in healthy persons. Further, a mouse having SITH-1 introduced therein developed a mental disorder such as a manic-depressive illness or depression-like disorder. Based on these findings, it is possible to provide a method for objectively determining a mental disorder and an animal model of a mental disorder.

1 - 23 . (canceled) 
     
     
         24 . A protein being:
 (a) a protein having the amino acid sequence shown in SEQ ID NO:  1 ;   (b) a protein having an amino acid sequence with a substitution, deletion insertion, and/or addition of five or less amino acids in the amino acid sequence shown in SEQ ID NO: 1, the protein having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand;   (c) a protein having, an amino acid sequence having at least 97% identity with the amino acid sequence shown in SEQ ID NO: 1, the protein having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand;   (d) a partial fragment of SEQ ID NO: 1 having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand;   (e) a protein encoded by a gene comprising an open reading frame region having the nucleotide sequence shown in SEQ ID NO: 2; or   (f) a protein encoded by a gene having a nucleotide sequence which is at least 97% identical to the nucleotide sequence shown in SEQ ID NO: 2, the protein having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand.   
     
     
         25 . A diagnosis kit suitable for performing a diagnosis method for diagnosing whether or not a human subject has a mood disorder, said method comprising the steps of:
 (i) determining, in a sample obtained from a human subject, a level of an antibody that recognizes the protein of  claim 24 ; and   (ii) determining that the human subject has a mood disorder, wherein step (i) then determines that the level of the antibody exists at a diagnostic level in the human subject, and   wherein the mood disorder is selected from the group consisting of depression and manic-depressive illness.   
     
     
         26 . A diagnosis kit suitable for performing a diagnosis method for diagnosing whether or not a human subject has a mood disorder, comprising:
 (i) a protein being:
 (a) a protein having the amino acid sequence shown in SEQ ID NO: 1; 
 (b) a protein having an amino acid sequence with a substitution, deletion, insertion, and/or addition of ten or less amino acids in the amino acid sequence shown in SEQ ID NO: 1, the protein having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand; 
 (c) a protein encoded by a gene comprising an open reading frame region having the nucleotide sequence shown in SEQ ID NO: 2; or 
 (d) a protein encoded by a gene having a nucleotide sequence which is at least 90% identical to the nucleotide sequence shown in SEQ ID NO: 2, the protein having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand; 
   (ii) a partial fragment of the protein (i) having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand; and   (iii) an instrument to which the protein (i) or the partial fragment (ii) is immobilized.   
     
     
         27 . A diagnosis kit suitable for performing a diagnosis method for diagnosing whether or not a non-human animal subject has a mood disorder, said method comprising the steps of:
 (i) determining, whether or not an antibody against a protein of  claim 24  exists in the non-human animal subject; and   (ii) determining that the non-human animal subject has a mood disorder, wherein step (i) then determines that the antibody exists at a diagnostic level in the non-human animal subject, and wherein the mood disorder is selected from the group consisting of depression and manic-depressive illness.   
     
     
         28 . The diagnosis kit as set forth in  claim 27 , comprising at least one selected from:
 (i) a protein being:
 (a) a protein having the amino acid sequence shown in SEQ ID NO: 1; 
 (b) a protein having an amino acid sequence with a substitution, deletion, insertion, and/or addition of ten or less amino acids in the amino acid sequence shown in SEQ ID NO: 1, the protein having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand; 
 (c) a protein encoded by a gene comprising an open reading frame region having the nucleotide sequence shown in SEQ ID NO: 2; or 
 (d) a protein encoded by a gene having a nucleotide sequence which is at least 90% identical to the nucleotide sequence shown in SEQ ID NO: 2, the protein having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand; 
   (ii) a partial fragment of the protein (i) having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand; and   (iii) an instrument to which the protein (i) or the partial fragment (ii) is immobilized.   
     
     
         29 . A diagnosis kit suitable for performing a diagnosis method for diagnosing whether or not a subject has a mood disorder, said method comprising the steps of:
 (i) determining, in a sample obtained from a subject, a level of the protein of  claim 24 ; and   (ii) determining that the subject has a mood disorder, in a case where step (i) determines that the level of the protein is at a diagnostic level in the subject, and   wherein the mood disorder is selected from the group consisting of depression and manic-depressive illness.   
     
     
         30 . The diagnosis kit as set forth in  claim 29 , comprising at least one selected from:
 (i) an antibody against a protein as set forth in  claim 24 ; and   (ii) an instrument to which the antibody is immobilized.   
     
     
         31 . A diagnosis kit suitable for performing a diagnosis method for diagnosing whether or not a human subject has a mood disorder, said method comprising the steps of:
 (i) determining, in the human subject, a level of an antibody that recognizes a protein being:
 (a) a protein having the amino acid sequence shown in SEQ ID NO: 1; 
 (b) a protein having an amino acid sequence with a substitution, deletion, insertion, and/or addition of ten or less amino acids in the amino acid sequence shown in SEQ ID NO: 1, the protein having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand; 
 (c) a protein encoded by a gene comprising an open reading frame region having the nucleotide sequence shown in SEQ ID NO: 2; or 
 (d) a protein encoded by a gene having a nucleotide sequence which is at least 90% identical to the nucleotide sequence shown in SEQ ID NO: 2, the protein having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand; and 
   (ii) determining whether or not the human subject has a mood disorder by using, as an indication, the level of the antibody that recognizes said protein in the human subject, and   wherein the mood disorder is selected from the group consisting of depression and manic-depressive illness.   
     
     
         32 . The diagnosis kit as set forth in  claim 31 , comprising at least one selected from:
 (i) a protein being:
 (a) a protein having the amino acid sequence shown in SEQ ID NO: 1; 
 (b) a protein having an amino acid sequence with a substitution, deletion, insertion, and/or addition of ten or less amino acids in the amino acid sequence shown in SEQ ID NO: 1, the protein having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand; 
 (c) a protein encoded by a gene comprising an open reading frame region having the nucleotide sequence shown in SEQ ID NO: 2; or 
 (d) a protein encoded by a gene having a nucleotide sequence which is at least 90% identical to the nucleotide sequence shown in SEQ ID NO: 2, the protein having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand; 
   (ii) a partial fragment of the protein (i) having activity of increasing an intracellular calcium concentration or activity of binding to calcium-modulating cyclophilin ligand; and   (iii) an instrument to which the protein (i) or the partial fragment (ii) is immobilized.   
     
     
         33 . The protein of  claim 24 , which is (a). 
     
     
         34 . The protein of  claim 24 , which is (b). 
     
     
         35 . The protein of  claim 24 , which is (c). 
     
     
         36 . The protein of  claim 24 , which is (d). 
     
     
         37 . The diagnosis kit of  claim 25 , further comprising instructions for performing said method. 
     
     
         38 . The kit of  claim 26 , wherein said protein is (a). 
     
     
         39 . The kit of  claim 26 , wherein said protein is (b). 
     
     
         40 . The kit of  claim 26 , wherein said protein is (c). 
     
     
         41 . The kit of  claim 26 , wherein said protein is (d). 
     
     
         42 . The kit of  claim 25 , further comprising reagents used for an immunological reaction. 
     
     
         43 . The kit of  claim 42 , wherein the immunological reaction is an enzyme-linked immunosorbent assay (ELISA).