Enterovirus 71 mutations associated with disease severity
A method of detecting severe disease-associated mutations in an enterovirus 71 (EV-A71), comprising: performing an assay on a test sample containing an EV-A71 genomic RNA, a fragment thereof or an amplicon thereof, or an EV-A71 VP1 protein or fragment thereof to detect one or more severe disease-associated mutations in the EV-A71 genomic RNA, the fragment thereof or the amplicon thereof, or the EV-A71 protein or fragment thereof, wherein the one or more mutations are selected from mutations at positions corresponding to 5′ UTR nucleotide positions C580, A707, and C709 in an EV-A71 5′ UTR nucleic acid sequence and at residues corresponding to A280 and E145 in an EV-A71 VP1 protein sequence.
1 . A method of detecting severe disease-associated mutations in an enterovirus 71 (EV-A71), comprising:
performing an assay on a test sample containing an EV-A71 genomic RNA, a fragment thereof or an amplicon thereof, or an EV-A71 VP1 protein or fragment thereof to detect one or more severe disease-associated mutations in the EV-A71 genomic RNA, the fragment thereof or the amplicon thereof, or the EV-A71 protein or fragment thereof,
wherein the one or more mutations are selected from mutations at positions corresponding to 5′ UTR nucleotide positions C580U, A707G, and C709U in an EV-A71 5′ UTR nucleic acid sequence and at residues corresponding to A280T in an EV-A71 VP1 protein sequence.
2 . The method of claim 1 , wherein the assay detects the one or more severe disease-associated mutations in the genome of the EV-A71 or one or more mutated amino acids in proteins resulting from the one or more severe disease-associated mutations.
3 . The method of claim 2 , wherein the assay is an immune assay or a PCR-based amplification followed by a sequencing assay.
4 . The method of claim 1 , wherein the test sample is prepared from a biological sample from a subject infected with the EV-A71.
5 . The method of claim 4 , wherein the biological sample contains a body fluid, tissue, or cell.
6 . The method of claim 5 , wherein the sample is a throat swab, cerebral spinal fluid (CSF) sample, blood sample, serum sample, plasma sample, tear sample, urine sample, nasal excretion sample, sputum sample, sperm sample, or feces sample.
7 . A method of assessing risk of developing a severe disease in a subject infected with an enterovirus 71 (EV-A71), comprising:
obtaining a test sample containing an EV-A71 genomic RNA, a fragment thereof or an amplicon thereof, or an EV-A71 VP1 protein or fragment thereof, wherein the test sample is prepared from a biological sample from a subject infected with the EV-A71; and
detecting in the test sample the presence of one or more of severe disease-associated mutations in the EV-A71 genomic RNA, the fragment thereof or the amplicon thereof, or the EV-A71 VP1 protein or fragment thereof, wherein the one or more mutations are selected from mutations at positions corresponding to 5′ UTR nucleotide positions C580U, A707G, and C709U in an EV-A71 5′ UTR nucleic acid sequence and at residues corresponding to A280T in an EV-A71 VP1 protein sequence;
wherein the presence of one or more of the mutations indicates a higher risk of developing a severe disease in the subject.
8 . The method of claim 7 , wherein the detecting step detects the one or more severe disease-associated mutations in the genome of the EV-A71 or one or more mutated amino acids in proteins resulting from the one or more severe disease-associated mutations.
9 . The method of claim 8 , wherein the detecting step includes performing an immune assay or a PCR-based amplification followed by a sequencing assay.
10 . The method of claim 7 , wherein the test sample is prepared from a biological sample from the subject that contains a body fluid, tissue, or cell.
11 . The method of claim 10 , wherein the sample is a throat swab, cerebral spinal fluid (CSF) sample, blood sample, serum sample, plasma sample, tear sample, urine sample, nasal excretion sample, sputum sample, sperm sample, or feces sample.
12 . A method of treating a subject infected with an enterovirus 71 (EV-A71), comprising:
obtaining a test sample containing an EV-A71 genomic RNA, a fragment thereof or an amplicon thereof, or an EV-A71 VP1 protein or fragment thereof, wherein the test sample is prepared from a biological sample from a subject infected with the EV-A71; and
detecting in the test sample the presence of one or more of severe disease-associated mutations in the EV-A71 genomic RNA, the fragment thereof or the amplicon thereof, or the EV-A71 VP1 protein or fragment thereof, wherein the mutations are selected from mutations at positions corresponding to 5′ UTR nucleotide positions C580U, A707G, and C709U in an EV-A71 5′ UTR nucleic acid sequence and at residues corresponding to A280T in an EV-A71 VP1 protein sequence; and
administering a treatment or treatment regimen for decreasing risk of development of a severe disease in the subject.
13 . The method of claim 12 , wherein the assay detects the one or more severe disease-associated mutations in the genome of the EV-A71 or mutated amino acids in proteins resulting from the one or more severe disease-associated mutations.
14 . The method of claim 12 , wherein the detecting step is carried out with an immune assay or PCR-based amplification followed by a sequencing assay.
15 . The method of claim 12 , wherein the biological sample contains a body fluid, tissue, or cell.
16 . The method of claim 15 , wherein the biological sample is a throat swab, cerebral spinal fluid (CSF) sample, blood sample, serum sample, plasma sample, tear sample, urine sample, nasal excretion sample, sputum sample, sperm sample, or feces sample.
17 . The method of claim 12 , wherein the severe disease is myoclonic jerks, meningitis, encephalitis, acute flaccid paralysis, tachycardia, pulmonary edema, cardiopulmonary failure, or death.