Interferon-λ4 (IFNL4) protein, related nucleic acid molecules, and uses thereof
The invention is related to identification of an interferon-analog (IFNL4) protein and genetic association with spontaneous clearance of HCV infection and response to treatment for HCV infection.
1. An isolated protein comprising the amino acid sequence of SEQ ID NO: 2 and at least one sequence feature selected from the group consisting of:
a. a cysteine residue at the position corresponding to position 27 of SEQ ID NO:2;
b. a leucine residue at the position corresponding to position 29 of SEQ ID NO:2
c. a serine residue at the position corresponding to position 30 of SEQ ID NO:2
d. a tyrosine residue at the position corresponding to position 32 of SEQ ID NO:2
e. a serine residue at the position corresponding to position 34 of SEQ ID NO:2
f. a proline residue at the position corresponding to position 37 of SEQ ID NO:2;
g. a leucine residue at the position corresponding to position 40 of SEQ ID NO:2;
h. an alanine residue at the position corresponding to position 42 of SEQ ID NO:2;
i. a lysine residue at the position corresponding to position 44 of SEQ ID NO:2;
j. an aspartic acid residue at the position corresponding to position 48 of SEQ ID NO:2;
k. a tyrosine residue at the position corresponding to position 50 of SEQ ID NO:2;
l. a leucine residue at the position corresponding to position 111 of SEQ ID NO:2;
m. a leucine residue at the position corresponding to position 112 of SEQ ID NO:2;
n. an aspartic acid residue at the position corresponding to position 118 of SEQ ID NO:2;
o. an alanine residue at the position corresponding to position 120 of SEQ ID NO:2;
p. a cysteine residue at the position corresponding to position 122 of SEQ ID NO:2;
q. a cysteine residue at the position corresponding to position 152 of SEQ ID NO:2;
r. a valine residue at the position corresponding to position 157 of SEQ ID NO:2;
s. an asparagine residue at the position corresponding to position 160 of SEQ ID NO:2;
t. a leucine residue at the position corresponding to position 161 of SEQ ID NO:2;
u. an arginine residue at the position corresponding to position 163 of SEQ ID NO:2
v. a leucine residue at the position corresponding to position 165 of SEQ ID NO:2;
w. a threonine residue at the position corresponding to position 166 of SEQ ID NO:2;
x. an alanine residue at the position corresponding to position 173 of SEQ ID NO:2; and
y. a cysteine residue at the position corresponding to position 178 of SEQ ID NO:2
wherein the isolated protein has at least one activity selected from the group consisting of eliciting an antibody that selectively binds a protein consisting of SEQ ID NO:2, selectively binding a compound that binds to a protein consisting of SEQ ID NO:2, activating expression of the JAK/STAT pathway, and inducing expression of at least one ISG listed in FIG. 15 .
2. An isolated protein, comprising the amino acid sequence of SEQ ID NO: 2 wherein the isolated protein has at least one sequence feature selected from the group consisting of:
(a) at least one amino acid substitution, as compared to SEQ ID NO:2, selected from A10P, A11P, L13M, V15F, C17Y, V19M, 120V, A21P, R26G, L28M, L35M, L40M, E52K, L55M, W57R, R60P, N61H, S63P, F64V, R65G, D69H, P70S, P71T, R72G, R78G, V92M, L93I, L101M, L102F, G116R, A121P, A126P, P128A, G129A, 5130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, K154E, A155P, S156G, V1581, F159V, L162M, L164M, and L169F;
(b) at least one amino acid substitution as compared to SEQ ID NO:2 selected from A10P, A11P, L13M, V15F, C17Y, V19M, 120V, A21P, R26G, L28M, L35M, L40M, E52K, L55M, W57R, R60P, N61H, S63P, F64V, R65G, D69H, P70S, P71T, R72G, G116R, A121P, A126P, P128A, G129A, 5130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, K154E, A155P, S156G, V1581, F159V, L162M, L164M, and L169F;
(c) has at least one amino acid substitution as compared to SEQ ID NO:2 selected from A10P, A11P, L13M, V15F, C17Y, V19M, 120V, A21P, R26G, L28M, L35M, L40M, G116R, A121P, A126P, P128A, G129A, 5130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, K154E, A155P, S156G, V1581, F159V, L162M, L164M, and L169F; or
(d) at least one amino acid substitution as compared to SEQ ID NO:2 selected from C27G, S34P, P37A, D48H, C62R, A87P, D118H, A120P, C122G, C152G, V157L, N160D, L161F, L164M, L165F, T166P, L169F, and A173P
wherein the isolated protein has at least one activity selected from the group consisting of eliciting an antibody that selectively binds a protein consisting of SEQ ID NO:2, selectively binding a compound that binds to a protein consisting of SEQ ID NO:2, activating expression of the JAK/STAT pathway, and inducing expression of at least one ISG listed in FIG. 15 .
3. The isolated protein of claim 1 , wherein the protein has been modified by at least one protein modification selected from pegylation, phosphorylation, acetylation, myristylation, palmitoylation, and amidation.
4. The isolated protein of claim 2 , wherein the protein has been modified by at least one protein modification selected from pegylation, phosphorylation, acetylation, myristylation, palmitoylation, and amidation.
5. An isolated protein comprising the amino acid sequence of SEQ ID NO: 2 modified by at least one protein modification selected from pegylation, phosphorylation, acetylation, myristylation, palmitoylation, and amidation,
wherein the isolated protein has at least one activity selected from the group consisting of eliciting an antibody that selectively binds a protein consisting of SEQ ID NO:2, selectively binding a compound that binds to a protein consisting of SEQ ID NO:2, activating expression of the JAK/STAT pathway, and inducing expression of at least one ISG listed in FIG. 15 .