Cryptic proteins expressed from defective viral genomes interfere with influenza virus replication
AssigneeWisconsin Alumni Research Foundation
InventorsAndrew Mehle, Jordan Ranum, Mitchell Ledwith
Life of this patent
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Abstract
The disclosure provides for methods for making and using modified influenza gene products, alone or in combination, e.g., to inhibit wild-type influenza virus replication, to serve as an immunostimulatory agent, and/or as attenuated vaccine backbones. In one embodiment, the genomes of the DIPs provide for inhibitory activity, producing a dual effect in which both the RNA itself and the encoded protein coordinate to interfere with replication. Thus, the ability of DIPs to block replication of WT virus provides for a treatment for infection, use as an immunostimulatory agent, and as attenuated viruses for vaccination.
Claims24
An isolated influenza virus comprising:
- i) 8 different gene segments including a PA viral gene segment, a PB1 viral gene segment, a mutant PB2 viral gene segment, a HA viral gene segment, a NA viral gene segment, a NP viral gene segment, a M (M1 and M2) viral gene segment, and a NS (NS1 and NS2) viral gene segment, or
- ii) 8 different gene segments including a PA viral gene segment, a PB1 viral gene segment, a mutant PB2 viral gene segment, a HA viral gene segment, a NA (NA and NB) viral gene segment, a NP viral gene segment, a M (M1 and BM2) viral gene segment and a NS (NS1 and NS2) viral gene segment;
- wherein the mutant PB2 viral gene segment includes 5′ and 3′ packaging sequences including 3′ or 5′ coding and non-coding packaging sequences flanking a nucleotide sequence having PB2 sequences that encode an inhibitory protein or a nucleotide sequence having PB2 sequences that encode a polypeptide having at least 5, 10, 15, 20, 25, 30, 35 or 39, or any integer between 1 and 40 N-terminal amino acids of PB2, wherein the mutant PB2 segment does not include contiguous sequences corresponding to sequences encoding a functional PB2.
An isolated nucleic acid comprising a nucleotide sequence encoding any one of SEQ ID Nos. 1 to 44, or a protein having at least 80%, 85%, 90%, 92%, 95%, 97% or 99% amino acid sequence identity thereto.
14-15. (canceled)
19-27. (canceled)
33-44. (canceled)
Dependencies are inferred from the claim text.