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AssigneesThe United States of America, as represented by the Secretary, Department of Health and Human Services, Royal Cornwall Hospital Trust
InventorsSuzanne U. Emerson, Priyanka Shukla, Hanh T. Nguyen, Robert H. Purcell, Harry R. Dalton, Richard Bendall
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The invention relates to the discovery of an HEV strain from a chronically infected patient. The virus grow unusually well in numerous cell cultures. Thus, the invention provides cell cultures, vectors, and vaccine compositions based on the virus. The invention relates, in part, on the identification of a new strain of HEV genotype 3 virus. Strain Kernow-C1 (genotype 3) of HEV, which was isolated from a chronically infected patient, was used to identify human, pig and deer cell lines permissive for infection. Adaptation of the Kernow-C 1 strain to growth in human hepatoma cells selected for a rare virus recombinant that contained an insertion of 174 ribonucleotides (58 amino acids) of a human ribosomal protein gene and additional mutations.
An infectious hepatitis E virus (HEV) type 3 cDNA clone, wherein the infectious clone comprises an insert, relative to the HEV nucleic acid sequence set forth in SEQ ID NO:5, in the region of the nucleic acid sequence that encodes the hypervariable region of ORF1, wherein the insert encodes an in-frame polypeptide sequence of 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, or 65 amino acids in length that has at least 85% identity to SEQ ID NO:9 over its length when maximally aligned to SEQ ID NO:9.
An infectious hepatitis E virus (HEV) cDNA clone, wherein the cDNA clone has at least 75% sequence identity to SEQ ID NO:1 and comprises an insert in the region of the nucleic acid sequence that encodes the hypervariable region of ORF1, relative to the HEV nucleic acid sequence set forth in SEQ ID NO:5, wherein the insert encodes an in-frame polypeptide sequence that is 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, or 65 amino acids in length and has at least 85% identity to SEQ ID NO:9 over its length when maximally aligned to SEQ ID NO:9.
An infectious genotype 3 or genotype 1 cDNA clone comprising a hepatitis E virus (HEV) nucleic acid sequence, wherein the infectious clone comprises an insert in the region of the nucleic acid sequence that encodes the hypervariable region of ORF1 and wherein the insert encodes an in-frame polypeptide sequence that is 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, or 65 amino acids in length and has at least 85% identity to SEQ ID NO:9 over its length when maximally aligned to SEQ ID NO:9.
Dependencies are inferred from the claim text.