Flavivirus host-range mutations and uses thereof
AssigneeResearch Development Foundation
InventorsDennis T. Brown, Raquel Hernandez
Life of this patent
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Abstract
Methods and compositions concerning mutant flaviviruses with host-range phenotypes are provided. Nucleotide sequences that encode mutant flavivirus proteins are also provided. In certain aspects, viruses comprising these sequences display reduced replication in mammalian cells. In further aspects of the invention, flavivirus vaccine compositions and methods for vaccination against flavivirus infection are provided.
Claims32
A modified flavivirus envelope protein (E) comprising a mutated E protein N-terminal transmembrane domain (E-T1 domain), such a mutation comprising a proline substituted for one or more amino acids at position 0, −1, −2, −3, −4, −6, −8, +2, +3, +4, +5, or +6 (wherein the central amino acid of the E-T1 domain is numbered position 0, amino acids proceeding toward the N terminus are numbered −1, −2, etc., and amino acids proceeding toward the C-terminus are numbered +1, +2, etc.), wherein the effective membrane-spanning distance of the mutated E-T1 domain is shorter than the effective membrane-spanning distance of a wild-type E-T1 domain, and a virus comprising the modified flavivirus E protein has an ability to infect mammalian cells but a reduced ability to replicate therein relative to wild-type virus.
Dependencies are inferred from the claim text.