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Connor G. G. Bamford, Elihu Aranday-Cortes, Ines Cordeiro Filipe, Swathi Sukumar, Daniel Mair, Ana da Silva Filipe, Juan L. Mendoza, K. Christopher Garcia, Shaohua Fan, Sarah A. Tishkoff, John McLauchlan
A polymorphic residue that attenuates the antiviral potential of interferon lambda 4 in hominid lineages
www.plospathogens.org
www.plospathogens.org
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(persistence)Tj
4.5694 0 Td
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1.0204 0 Td
(HCV)Tj
2.3244 0 Td
(infection)Tj
3.7304 0 Td
(is)Tj
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(not)Tj
1.5477 0 Td
(well)Tj
1.7915 0 Td
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(but)Tj
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(associated)Tj
-33.613 -1.3039 Td
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(enhanced)Tj
4.0308 0 Td
(ISG)Tj
1.7291 0 Td
(induction.)Tj
4.303 0 Td
(Moreover,)Tj
4.3426 0 Td
(a)Tj
0.6463 0 Td
(common)Tj
3.8098 0 Td
(natural)Tj
3.0387 0 Td
(variant)Tj
2.9877 0 Td
(of)Tj
1.0034 0 Td
(HsIFN)Tj
/F12 1 Tf
()Tj
/F7 1 Tf
(4)Tj
3.8835 0 Td
(\(P70S\))Tj
2.8459 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(],)Tj
-34.5937 -1.2982 Td
(which)Tj
2.6191 0 Td
(has)Tj
1.5251 0 Td
(reduced)Tj
3.4015 0 Td
(signalling)Tj
4.0082 0 Td
(capacity,)Tj
3.6453 0 Td
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(also)Tj
1.7404 0 Td
(linked)Tj
2.6929 0 Td
(with)Tj
1.9786 0 Td
(improved)Tj
4.0592 0 Td
(HCV)Tj
2.3244 0 Td
(clearance)Tj
3.8948 0 Td
([)Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(].)Tj
2.0466 0 Td
(Thus,)Tj
-34.7752 -1.2983 Td
(there)Tj
2.2336 0 Td
(is)Tj
0.8334 0 Td
(a)Tj
0.652 0 Td
(spectrum)Tj
3.9118 0 Td
(of)Tj
1.0034 0 Td
(HsIFN)Tj
/F12 1 Tf
()Tj
/F7 1 Tf
(4)Tj
3.8835 0 Td
(activity)Tj
3.067 0 Td
(in)Tj
1.0262 0 Td
(humans)Tj
3.4015 0 Td
(as)Tj
1.0035 0 Td
(a)Tj
0.6463 0 Td
(consequence)Tj
5.2724 0 Td
(of)Tj
1.0034 0 Td
(natural)Tj
3.0388 0 Td
(variation)Tj
3.7473 0 Td
(that)Tj
-34.7241 -1.3039 Td
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1.5136 0 Td
(a)Tj
0.6407 0 Td
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4.3143 0 Td
(influence)Tj
3.8494 0 Td
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1.2586 0 Td
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3.2371 0 Td
(HCV)Tj
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3.9458 0 Td
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1.9616 0 Td
(wt)Tj
1.1849 0 Td
(HsIFN)Tj
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()Tj
/F7 1 Tf
(4)Tj
3.8721 0 Td
(representing)Tj
5.159 0 Td
(the)Tj
1.44 0 Td
(protein)Tj
-34.6958 -1.2983 Td
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(apparently)Tj
4.405 0 Td
(the)Tj
1.4513 0 Td
(greatest)Tj
3.2485 0 Td
(antiviral)Tj
3.4866 0 Td
(activity.)Tj
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-13.3681 -1.2983 Td
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3.7587 0 Td
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2.3471 0 Td
(human)Tj
3.0784 0 Td
(IFN)Tj
/F12 1 Tf
()Tj
/F7 1 Tf
(4)Tj
2.8006 0 Td
(variants)Tj
3.3845 0 Td
(exist)Tj
2.0353 0 Td
(in)Tj
1.0375 0 Td
(addition)Tj
3.5999 0 Td
(to)Tj
1.0205 0 Td
(P70S,)Tj
2.4321 0 Td
(which)Tj
2.6532 0 Td
(affect)Tj
2.3754 0 Td
(antiviral)Tj
3.5377 0 Td
(activ-)Tj
-35.2571 -1.3039 Td
(ity,)Tj
1.4569 0 Td
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1.5364 0 Td
(not)Tj
1.5704 0 Td
(been)Tj
2.1146 0 Td
(explored)Tj
3.6964 0 Td
(fully.)Tj
2.2053 0 Td
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(this)Tj
1.6667 0 Td
(study,)Tj
2.6136 0 Td
(we)Tj
1.3209 0 Td
(have)Tj
2.0523 0 Td
(examined)Tj
4.1215 0 Td
(human)Tj
3.0727 0 Td
(genetic)Tj
3.0671 0 Td
(data)Tj
1.9049 0 Td
(to)Tj
1.0204 0 Td
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(possible)Tj
3.4072 0 Td
(naturally)Tj
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(occurring)Tj
4.1273 0 Td
(IFN)Tj
/F12 1 Tf
()Tj
/F7 1 Tf
(4)Tj
2.7949 0 Td
(variants)Tj
3.3902 0 Td
(and)Tj
1.7291 0 Td
(performed)Tj
4.4731 0 Td
(comparative)Tj
5.1703 0 Td
(analysis)Tj
3.3222 0 Td
(with)Tj
-34.5427 -1.2983 Td
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5.0399 0 Td
(orthologues)Tj
4.9606 0 Td
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1.0205 0 Td
(humans.)Tj
3.668 0 Td
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1.6101 0 Td
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3.2881 0 Td
(evidence)Tj
3.7077 0 Td
(that)Tj
1.7802 0 Td
(the)Tj
-34.9396 -1.3039 Td
(antiviral)Tj
3.5376 0 Td
(potential)Tj
3.7644 0 Td
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1.3832 0 Td
(the)Tj
1.4684 0 Td
(most)Tj
2.211 0 Td
(common)Tj
3.8438 0 Td
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2.2053 0 Td
(of)Tj
1.0148 0 Td
(IFN)Tj
/F12 1 Tf
()Tj
/F7 1 Tf
(4)Tj
2.7949 0 Td
(in)Tj
1.0375 0 Td
(humans)Tj
3.4356 0 Td
(has)Tj
1.542 0 Td
(attenuated)Tj
4.439 0 Td
(activity)Tj
3.1181 0 Td
(due)Tj
-35.7956 -1.2983 Td
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1.0261 0 Td
(a)Tj
0.6519 0 Td
(single)Tj
2.5342 0 Td
(amino)Tj
2.7949 0 Td
(acid)Tj
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(substitution.)Tj
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3.8268 0 Td
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1.3266 0 Td
(propose)Tj
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(that)Tj
1.7745 0 Td
(acquisition)Tj
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(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(attenuating)Tj
-32.6662 -1.2982 Td
(substitution)Tj
4.9889 0 Td
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2.3131 0 Td
(very)Tj
1.9275 0 Td
(early)Tj
2.1486 0 Td
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2.9254 0 Td
(human)Tj
3.0784 0 Td
(evolution)Tj
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(but)Tj
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1.7801 0 Td
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(do)Tj
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(encode)Tj
3.0784 0 Td
(a)Tj
-36.3285 -1.2983 Td
(more)Tj
2.3414 0 Td
(active)Tj
2.5171 0 Td
(variant.)Tj
3.2542 0 Td
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6.6953 0 Td
(our)Tj
1.6271 0 Td
(data)Tj
1.9106 0 Td
(show)Tj
2.3017 0 Td
(that)Tj
1.7801 0 Td
(the)Tj
1.4684 0 Td
(reduced)Tj
3.4469 0 Td
(antiviral)Tj
3.5376 0 Td
(potential)Tj
3.7644 0 Td
(of)Tj
-34.6448 -1.3039 Td
(human)Tj
3.0784 0 Td
(IFN)Tj
/F12 1 Tf
()Tj
/F7 1 Tf
(4)Tj
2.7949 0 Td
(results)Tj
2.8063 0 Td
(from)Tj
2.2053 0 Td
(a)Tj
0.6577 0 Td
(likely)Tj
2.3527 0 Td
(dual)Tj
1.9559 0 Td
(defect)Tj
2.6022 0 Td
(in)Tj
1.0375 0 Td
(secretion)Tj
3.8437 0 Td
(and)Tj
1.7291 0 Td
(potency.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 442.9984 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Results)Tj
/F13 1 Tf
0 -1.4976 Td
(Functional)Tj
4.7433 0 Td
(consequences)Tj
5.8441 0 Td
(of)Tj
1.063 0 Td
(human)Tj
3.1843 0 Td
(IFN)Tj
/F14 1 Tf
()Tj
/F13 1 Tf
(4)Tj
2.9055 0 Td
(non-synonymous)Tj
7.4269 0 Td
(variation)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 408.0188 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
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(Firstly,)Tj
2.9593 0 Td
(we)Tj
1.3209 0 Td
(undertook)Tj
4.4164 0 Td
(genetic)Tj
3.0614 0 Td
(and)Tj
1.7178 0 Td
(functional)Tj
4.3029 0 Td
(comparisons)Tj
5.3235 0 Td
(of)Tj
1.0091 0 Td
(natural)Tj
3.0671 0 Td
(human)Tj
3.067 0 Td
(IFN)Tj
/F12 1 Tf
()Tj
/F7 1 Tf
(4)Tj
2.7893 0 Td
(coding)Tj
2.948 0 Td
(var-)Tj
-35.9827 -1.3039 Td
(iants)Tj
2.1259 0 Td
(present)Tj
3.1635 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(human)Tj
3.0784 0 Td
(population.)Tj
4.8188 0 Td
(We)Tj
1.6044 0 Td
(identified)Tj
4.0592 0 Td
(15)Tj
1.1736 0 Td
(non-synonymous)Tj
7.2623 0 Td
(HsIFN)Tj
/F12 1 Tf
()Tj
/F7 1 Tf
(4)Tj
3.9288 0 Td
(variants)Tj
-33.7207 -1.2982 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(1000)Tj
2.1203 0 Td
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4.0195 0 Td
(Project)Tj
3.0614 0 Td
(Database)Tj
3.8437 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(])Tj
1.8539 0 Td
(\()Tj
0.83 0.64 0.02 0 k
/F13 1 Tf
(Fig)Tj
1.8822 0 Td
(1A)Tj
0 g
1.4229 0 Td
(and)Tj
0.83 0.64 0.02 0 k
1.7915 0 Td
(S1)Tj
1.2132 0 Td
(Data)Tj
0 g
/F7 1 Tf
(\),)Tj
2.812 0 Td
(including)Tj
4.0422 0 Td
(three)Tj
2.262 0 Td
(previously)Tj
-32.8306 -1.2983 Td
(described)Tj
4.0535 0 Td
(variants)Tj
3.3845 0 Td
(\(C17Y,)Tj
3.0331 0 Td
(P60R)Tj
2.3527 0 Td
(and)Tj
1.7291 0 Td
(P70S;)Tj
/F15 1 Tf
0 Tc
2.4321 0 Td
(>)Tj
/F7 1 Tf
-0.004 Tc
(1%)Tj
2.2224 0 Td
(global)Tj
2.6249 0 Td
(frequency,)Tj
4.4163 0 Td
(classified)Tj
3.8211 0 Td
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(`common'\))Tj
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([)Tj
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(18)Tj
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(remaining)Tj
4.3653 0 Td
(12)Tj
1.1736 0 Td
(variants)Tj
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(classified)Tj
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(rare)Tj
1.8198 0 Td
(\()Tj
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0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(1%)Tj
2.5625 0 Td
(global)Tj
2.6249 0 Td
(frequency\).)Tj
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1.7858 0 Td
(African)Tj
3.2371 0 Td
(popula-)Tj
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(the)Tj
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(largest)Tj
2.8177 0 Td
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3.3902 0 Td
(\(A8S,)Tj
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(S56R)Tj
2.2677 0 Td
(and)Tj
1.7291 0 Td
(L79F\))Tj
2.5795 0 Td
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2.1203 0 Td
(shared)Tj
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(exclusively)Tj
4.5127 0 Td
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(American)Tj
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5.176 0 Td
(which)Tj
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2.058 0 Td
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3.8437 0 Td
(recent)Tj
2.7099 0 Td
(movements)Tj
4.8756 0 Td
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1.0148 0 Td
(people)Tj
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3.4412 0 Td
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1.474 0 Td
(transatlantic)Tj
5.1817 0 Td
(slave)Tj
2.1373 0 Td
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-11.038 -1.2983 Td
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1.0374 0 Td
(regions)Tj
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(of)Tj
1.0148 0 Td
(functional)Tj
4.3086 0 Td
(significance)Tj
4.9379 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(HsIFN)Tj
/F12 1 Tf
()Tj
/F7 1 Tf
(4)Tj
3.9232 0 Td
(protein)Tj
3.1521 0 Td
(\()Tj
0.83 0.64 0.02 0 k
/F13 1 Tf
(Fig)Tj
1.8822 0 Td
(1B)Tj
0 g
-35.9544 -1.2983 Td
(and)Tj
0.83 0.64 0.02 0 k
1.7914 0 Td
(S1AS1C)Tj
4.0932 0 Td
(Fig)Tj
0 g
/F7 1 Tf
(\),)Tj
2.109 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(predicted)Tj
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(signal)Tj
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(peptide)Tj
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(acids)Tj
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(124\),)Tj
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(glycosylation)Tj
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(site)Tj
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(\(N61\))Tj
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([both)Tj
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2.6532 0 Td
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(protein],)Tj
3.7133 0 Td
(and)Tj
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(helix)Tj
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(F)Tj
0.7483 0 Td
(that)Tj
1.7802 0 Td
(is)Tj
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(to)Tj
1.0261 0 Td
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3.2825 0 Td
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1.9956 0 Td
(the)Tj
1.4683 0 Td
(IFN)Tj
/F12 1 Tf
()Tj
/F7 1 Tf
(R1)Tj
3.4186 0 Td
(receptor)Tj
3.5603 0 Td
(\(variants)Tj
3.7247 0 Td
(151158\))Tj
3.9345 0 Td
([)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(].)Tj
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-34.0098 -1.2983 Td
(ingly,)Tj
2.4264 0 Td
(the)Tj
1.4683 0 Td
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(F)Tj
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(the)Tj
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(that)Tj
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(typic)Tj
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(effects)Tj
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(on)Tj
1.2755 0 Td
(HsIFN)Tj
/F12 1 Tf
()Tj
/F7 1 Tf
(4)Tj
3.9288 0 Td
(function.)Tj
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(note,)Tj
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(which)Tj
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(pre-)Tj
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1.0205 0 Td
(interaction)Tj
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1.9955 0 Td
(the)Tj
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(IL-10R2)Tj
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(receptor,)Tj
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(the)Tj
1.4684 0 Td
(IL-10R2-interacting)Tj
-28.8735 -1.304 Td
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