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[(high)-470(prevalence)-469.8(of)]TJ
/F9 1 Tf
8.9785 0 TD
[(Culex)-466(Univittatus)]TJ
/F4 1 Tf
7.5432 0 TD
[(,)-464.5(which)-466.5(was)-464(the)-465.3(main)]TJ
-16.5218 -1.2203 TD
[(vector)-465.4(\()-89(McIntosh)-466.8(et)-461.9(al.)-461.2(1976\).)-463(This)-466.5(mosquito)-463.1(is)-466.4(also)-462.4(likely)]TJ
T*
[(responsible)-673.4(for)-674.2(sporadic)-669.1(cases)-665.2(in)-670.8(interepidemic)-673.6(periods.)]TJ
T*
[(Seroprevalence)-503.3(investigations)-502.5(in)-493.8(the)-496.9(1950s1970s)-491.4(in)-493.8(South)]TJ
0 -1.2266 TD
[(Africa)-352.7(indicated)-350.7(that)-351.6(17%)-348.4(of)-351(people)-350.3(in)-348.4(the)-351.5(Karoo,)-346.6(8%)-348.9(in)-348.4(the)]TJ
0 -1.2203 TD
[(Highveld,)-192.1(and)-189.3(2%)-190.8(in)-190.3(Natal)-186.4(had)-189.3(antibodies)-192.6(for)-187.3(WNV)-191.5(outside)-189.4(of)]TJ
T*
[(epidemics)-338.2(\()-89(McIntosh)-334(et)-335.5(al.)-334.8(1976\).)-336.6(No)-331.5(recent)-338.8(serological)-337.4(data)]TJ
0 -1.2266 TD
[(are)-246.7(available.)-244.7(An)-238.7(epizootic)-247.1(involving)-247.4(WNV)-242.1(and)-239.8(Sindbis)-245.3(virus)]TJ
0 -1.2203 TD
[(was)-173.2(also)-171.5(reported)-179.5(in)-171.3(the)-174.5(1980s)-170.1(in)-171.3(the)-174.5(Witwatersrand)-177.5(area)-170.3(of)-174(the)]TJ
T*
[(Gauteng)-229.1(Province)-220.3(in)-221.9(South)-227.8(Africa,)-222.8(and)-220.9(this)-223.7(affected)-224.3(hundreds)]TJ
0 -1.2266 TD
[(of)-281.4(people)-287(\()-126.9(Jupp)-282.7(2001\).)]TJ
1.1128 -1.2203 TD
[(Since)-516.7(then,)-522.2(the)-515.9(number)-519.5(of)-515.4(conrmed)-515.4(human)-517.4(cases)-519.8(per)]TJ
-1.1128 -1.2203 TD
[(annum)-194.9(ranged)-188(from)-184.9(5)-189.2(t)0(o)-186.6(15.)-185.3(It)-192.3(is,)-184.8(however,)-195.3(suspected)-191.2(that)-187.2(only)]TJ
0 -1.2267 TD
[(a)-189.2(proportion)-196.9(of)-186.6(cases)-191(are)-189.8(subjected)-191.6(to)-192.9(laboratory)-189.5(investigation.)]TJ
0 -1.2203 TD
[(Despite)-267.1(the)-263(low)-260.8(number)-260.2(of)-262.5(reported)-261.7(cases,)-263.5(severe)-261.7(disease)-261.4(has)]TJ
T*
[(been)-279.5(recognized)-269.3(in)-278.8(Southern)-276(Africa,)-273.4(including)-272(fatal)-275.4(hepatitis;)]TJ
T*
[(several)-315.4(nonfatal)-316.5(encephalitis)-316.3(cases)-311.1(in)-310.4(humans;)-312.9(and)-315.7(deaths)-311.1(in)]TJ
0 -1.2266 TD
[(an)-230.5(ostrich)-232.8(chick,)-227.8(a)-227.1(foal,)-224.2(and)-227.2(a)-227.1(dog)-225.2(\(Burt)-233.6(et)-228(al.)-227.3(2002,)-222.3(Botha)-230.4(et)-228(al.)]TJ
0 -1.2203 TD
(2008\).)Tj
/F3 1 Tf
0 -2.447 TD
[(WNV)-337.3(in)-338(Horses)-332.2(in)-331.6(South)-339.4(Africa)]TJ
/F4 1 Tf
1.1128 -1.8336 TD
[(A)-349.2(serologic)-353.3(survey)-349.9(carried)-348.1(out)-346(in)-348.4(thoroughbred)-356.1(horses)-350.8(in)]TJ
-1.1128 -1.2203 TD
[(2003)-339.5(conrmed)-344.7(that)-339(WNV)-336.9(is)-340(widely)-344.8(distributed)-337.8(throughout)]TJ
T*
[(South)-392.2(Africa)-390.6(with)-388.4(11%)-386.3(of)-382.6(yearlings)-387.4(and)-391.6(up)-382.1(to)-388.9(75%)-386.3(of)-388.9(their)]TJ
0 -1.2266 TD
[(dams)-317.5(being)-319.2(exposed)-320.2(\(Guthrie)-318.4(et)-322.8(al.)-315.8(2003\).)-311.3(After)-319.1(the)-319.9(study,)-317(it)]TJ
0 -1.2203 TD
[(was)-356.5(postulated)-361.4(that)-357.9(endemic)-360.6(lineage)-361.9(2)-353.6(WNV)-355.9(strains)-358(do)-359.9(not)]TJ
T*
[(cause)-608.4(neuroinvasive)-615.1(disease)-602.8(in)-607.6(horses,)-606.7(because)-612.7(all)-600.9(these)]TJ
T*
[(horses)-293.9(were)-286.7(healthy)-286.5(with)-287.2(no)-290.7(record)-290.9(of)-281.4(disease.)-289.6(In)-290(addition,)-287.7(2)]TJ
0 -1.2266 TD
[(sero-negative)-516.5(horses)-508.9(were)-508(inoculated)-503.6(with)-508.5(a)-505.3(recent)-509.5(WNV)]TJ
0 -1.2203 TD
[(lineage)-305(2)-296.7(strain)-306.1(\(SPU381/00\))-299.9(from)-298.7(a)-303(person)-300.3(with)-299.9(benign)-303.6(dis-)]TJ
T*
[(ease)-234.6(and)-233.5(did)-224.5(not)-234.3(develop)-232.5(clinical)-230.6(signs.)-231.9(However,)-236.2(subsequent)]TJ
0 -1.2267 TD
[(studies)-365(have)-357.6(shown)-360.3(that)-364.2(SPU381/00)-355.9(is)-358.9(a)-359.9(mild)-355.4(strain)-363(of)-357.3(low)]TJ
/F3 1 Tf
-27.9978 77.2217 TD
(660)Tj
41.3455 0 TD
[(VENTER)-340.1(AND)-330.9(SWANEPOEL)]TJ
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/F4 1 Tf
8.9663 0 0 8.9663 59.7543 725.7825 Tm
0 0 0 rg
0 Tc
0 Tw
[(neuroinvasiveness)-216.4(in)-209.3(mice)-208.9(compared)-206.4(with)-205(certain)-209.1(other)-209.6(South)]TJ
0 -1.2203 TD
[(African)-273.8(strains)-275.8(\(Venter)-273.2(et)-272.3(al.)-265.2(2005\).)-273.3(Today,)-268.5(it)-269.6(is)-270.4(also)-272.7(clear)-268.5(that)]TJ
0 -1.2266 TD
[(subclinical)-541.2(cases)-538.8(are)-531.2(frequently)-543.4(reported)-533.6(in)-538(horses)-540.5(in)-531.7(the)]TJ
0 -1.2203 TD
[(United)-315.2(States)-310(\(Nielsen)-315.5(et)-310.2(al.)-309.5(2008\).)-311.3(In)-309(addition,)-313(experimental)]TJ
T*
[(infection)-421.4(of)-414.2(12)-416.3(horses)-420.4(with)-413.7(the)-421.1(highly)-414.7(neuroinvasive)-419.1(NY99)]TJ
0 -1.2266 TD
[(strain)-350.4(resulted)-357.9(in)-348.4(neuroinvasive)-349.6(disease)-356.2(in)-348.4(only)-349.2(one)-347.5(animal,)]TJ
0 -1.2203 TD
[(with)-502.2(the)-496.9(rest)-495.6(failing)-498.9(to)-496.4(develop)-498.1(clinical)-502.5(signs)-494.5(despite)-502.7(ser-)]TJ
T*
[(oconverting)-286.9(\(Bunning)-282.2(et)-284.9(al.)-277.8(2002,)-279.2(Nielsen)-283.4(et)-284.9(al.)-277.8(2008\).)]TJ
1.1128 -1.2266 TD
[(This)-257.8(raised)-254.6(the)-250.3(question)-257.4(whether)-256(neurological)-258.7(disease)-255.1(may)]TJ
-1.1128 -1.2203 TD
[(be)-225.6(missed)-227.9(in)-221.9(horses)-224.4(in)-228.2(South)-221.4(Africa.)-229.1(To)-220.8(address)-230(this,)-220.3(79)-226.6(serum)]TJ
T*
[(or)-439.7(brain)-441.5(specimens)-437.5(from)-437.8(horses)-439.3(that)-440.1(presented)-446.2(with)-439(unex-)]TJ
T*
[(plained)-355.7(fever)-355.8(\(48\))-360.4(and/or)-353.8(neurological)-359.8(symptoms)-354.5(\(31\))-354(were)]TJ
0 -1.2266 TD
[(screened)-209.7(over)-200.1(a)-201.8(period)-207.3(of)-199.3(18)-201.4(months)-204.9(for)-199.9(WNV)-204.2(by)-204.8(RT-PCR)-203.1(and)]TJ
0 -1.2203 TD
[(WNV)-229.4(IgM)-226.6(ELISA,)-225.9(and)-227.2(this)-223.7(was)-230.1(followed)-226.3(by)-223.8(plaque)-225.1(reduction)]TJ
T*
[(neutralization)-293.5(tests)-294.3(\(Venter)-292.2(et)-284.9(al.)-290.5(2009b\).)-284.1(WNV)-292.7(infection)-288.6(was)]TJ
0 -1.2266 TD
[(identied)-310.6(in)-297.8(6)-303(out)-301.8(of)-306.7(31)-302.5(neurological)-302.9(cases)-304.8(\(19%\),)-301.7(of)-300.4(which)-308.4(5)]TJ
0 -1.2203 TD
[(cases)-576.7(were)-571.2(fatal)-572.6(or)-572.5(had)-575(to)-572.3(be)-567.1(euthanized.)-579.6(Clinical)-572.9(signs)]TJ
T*
[(included)-377.4(ataxia,)-368(weak)-372.2(hinds)-368.7(and/or)-372.8(forelimbs,)-371.2(and)-372.6(paresis;)]TJ
0 -1.2266 TD
[(complete)-346.2(paralysis;)-346.9(seizures)-342.6(and)-341(chewing;)-347.2(partial)-343.7(blindness;)]TJ
0 -1.2203 TD
[(jaundice)-546(and/or)-537.2(hepatitis;)-541.2(and)-543.3(myosis)-535.7(of)-540.7(the)-541.2(pupils.)-540.2(Re-)]TJ
T*
[(cumbency,)-252.8(muscle)-255.9(twitching,)-257(chewing)-249.5(ts,)-254.3(and)-252.5(seizures)-254.1(were)]TJ
T*
[(observed)-221.4(in)-215.6(certain)-215.4(fatal)-218.5(cases.)-212.9(Coinfection)-222(with)-217.7(African)-216.9(horse)]TJ
0 -1.2266 TD
[(sickness)-292.7(virus)-285.9(\(AHSV\))-294.5(was)-287(detected)-290.4(in)-285.1(two)-289.4(cases)-285.8(and)-290.4(proba-)]TJ
0 -1.2203 TD
[(bly)-423.4(increased)-421.5(the)-421.1(severity)-422(of)-420.6(disease.)-422.4(Cases)-425.8(came)-419.9(from)-418.8(the)]TJ
T*
[(Gauteng-)-362.4(and)-353.7(North)-361.4(West)-354.8(and)-353.7(the)-357.8(Western)-358.8(Cape)-355(Provinces)]TJ
0 -1.2266 TD
[(of)-490.1(South)-493.3(Africa)-485.4(\(Venter)-494.5(et)-487.2(al.)-486.5(2009b\))-489.8(as)-487.7(well)-482.8(as)-487.7(Tanzania)]TJ
0 -1.2203 TD
[(\(Unpublished)-482.3(data\).)-473.8(All)-476.4(three)-472.2(RT-PCR-positive)-482.8(cases)-475.5(were)]TJ
T*
[(shown)-423.5(to)-420.6(belong)-416.8(to)-420.6(lineage)-425.2(2)-416.8(b)0(y)-419.8(DNA)-420.1(sequencing)-419.2(\(Venter)]TJ
0 -1.2266 TD
[(et)-272.3(al.)-271.5(2009b\),)-271.4(and)-277.8(this)-267.9(held)-275.4(good)-272.2(even)-275.8(with)-274.6(regard)-267.5(to)-275.1(the)-275.6(case)]TJ
0 -1.2203 TD
[(from)-286(Tanzania)-276.9(\(unpublished)-286.3(data\).)]TJ
1.1128 -1.2203 TD
[(The)-537.4(WNV)-532.9(positive)-538.4(horses)-534.2(were)-539.6(also)-531.9(tested)-536.2(for)-535.1(AHSV,)]TJ
-1.1128 -1.2266 TD
[(equine)-183.2(encephalosis)-189.9(virus,)-181.3(and)-182.9(equine)-183.2(herpes)-183.6(virus)-178.4(plus)-184.6(rabies)]TJ
0 -1.2203 TD
[(in)-335.7(severe)-337.6(fatal)-338.6(cases.)-339.4(The)-335.1(AHSV)-337.8(was)-337.6(detected)-334.7(in)-335.7(two)-340(horses)]TJ
T*
[(with)-205(fatal)-199.5(disease;)-201.1(however,)-201.6(four)-201.3(were)-198.1(only)-203.8(positive)-197(for)-206.3(WNV,)]TJ
T*
[(whereas)-341.4(none)-338.2(of)-338.4(the)-338.9(other)-342.3(viruses)-337.6(were)-337.2(detected.)-337.6(Three)-342(RT-)]TJ
0 -1.2266 TD
[(PCR)-328.2(positive)-336.1(cases)-323.8(were)-330.9(sequenced)-334.9(and)-322(shown)-335(to)-325.7(belong)-328.3(to)]TJ
0 -1.2203 TD
[(lineage)-210.2(2)-201.8(o)0(n)-202.2(the)-206.1(basis)-206.1(of)-205.6(the)-206.1(nonstructural)-207.9(5)-208.2(\(NS5\))-207.6(gene.)-200.2(The)]TJ
/F9 1 Tf
25.8164 0 TD
(E)Tj
/F4 1 Tf
.6007 0 TD
(,)Tj
/F9 1 Tf
-26.4171 -1.2203 TD
(C)Tj
/F4 1 Tf
.6702 0 TD
[(,)-255.8(and)]TJ
/F9 1 Tf
2.4406 0 TD
(NS)Tj
/F4 1 Tf
1.3215 0 TD
[(5)-258.8(genes)-261.8(of)-262.5(virus)-260.6(isolated)-260.6(from)-260.7(the)-256.7(brain)-258.1(of)-262.5(one)-259(fatal)]TJ
-4.4324 -1.2266 TD
[(case)-430(were)-419.4(sequenced)-429.8(and)-423.2(shown)-429.8(to)-420.6(be)-427.9(closely)-425.7(related)-424.3(to)-426.9(a)]TJ
0 -1.2203 TD
[(lineage)-336.6(2)-328.3(strain)-331.4(isolated)-336.5(from)-330.3(humans)-329(with)-337.8(encephalitic)-333.2(dis-)]TJ
T*
[(ease)-304.1(in)-304.1(South)-310(Africa.)-305(These)-304.7(ndings)-306.6(conrm)-303.9(that)-301(WNV)-305.3(line-)]TJ
0 -1.2266 TD
[(age)-471.7(2)-473.7(causes)-470.6(fatal)-471.4(neurological)-473.6(disease)-476.4(in)-468.5(horses)-477.3(in)-468.5(South)]TJ
0 -1.2203 TD
[(Africa,)-298.7(and)-296.8(cases)-298.5(may)-292.3(have)-294.4(been)-298.5(previously)-297.8(missed.)-300.4(Human)]TJ
T*
[(and)-385.3(horse)-381.1(cases)-380.7(may)-380.9(be)-383.7(underdetected,)-383.9(and)-379(horses)-388.8(may)-374.5(be)]TJ
T*
[(useful)-292.5(sentinels)-294.9(to)-287.8(detect)-293.9(virus)-292.2(activity)-290.2(in)-285.1(the)-294.6(absence)-285.9(of)-294.1(bird)]TJ
0 -1.2266 TD
[(deaths)-285.8(in)-278.8(South)-284.7(Africa)-283.1(\(Venter)-285.8(et)-278.6(al.)-284.2(2009b\).)]TJ
/F3 1 Tf
0 -3.054 TD
[(Comparison)-335.9(of)-336.6(Mouse)-337.9(Gene)-333.7(Expression)-333.9(Following)]TJ
0 -1.2203 TD
[(Neuroinvasive)-338.6(Strains)-334.9(in)-331.6(Both)-338.7(Lineages)]TJ
/F4 1 Tf
1.1128 -1.8336 TD
[(To)-480(identify)-480.3(candidate)-479.5(host)-482.2(genes)-476.8(associated)-484.8(with)-476.9(WNV)]TJ
-1.1128 -1.2266 TD
[(pathogenesis,)-669.1(DNA)-660.4(microarray)-666.3(technology)-663(was)-660(used)-663.2(to)]TJ
0 -1.2203 TD
[(measure)-461.8(gene)-462.8(expression)-458.9(levels)-464.2(in)-455.8(brain,)-457.1(liver,)-460.2(and)-461.2(spleen)]TJ
T*
[(tissues)-413.9(of)-414.2(mice)-411.3(infected)-414.6(with)-413.7(WNV)-406.5(lineage)-412.5(1)-410.5(and)-410.6(2)-410.5(strains)]TJ
0 -1.2266 TD
[(\(Venter)-298.5(et)-291.2(al.)-284.2(2005\).)-292.3(The)-290.8(six)-291.5(strains)-288.4(selected)-298.1(in)-291.4(this)-286.9(study)-295.1(had)]TJ
0 -1.2203 TD
[(caused)-238.3(either)-235.5(severe)-236.4(or)-237.4(benign)-234(infection)-238(in)-234.5(humans)-234.1(and)-233.5(birds,)]TJ
T*
[(whereas)-240.3(the)-244(seventh)-236.7(strain)-242.9(was)-236.4(a)-233.5(mosquito)-241.8(isolate.)-241.6(All)-236.1(strains)]TJ
T*
[(were)-501.6(characterized)-501.9(as)-494(highly)-496.9(or)-496.7(less)-499.2(neuroinvasiveness)-507.2(in)]TJ
0 -1.2266 TD
[(mice,)-509(and)-505.4(highly)-509.5(neuroinvasive)-514(strains)-509.7(were)-508(identied)-512.9(in)]TJ
0 -1.2203 TD
[(lineage)-324(1)-315.7(and)-315.7(2.)-318.6(The)-322.4(WNV)-318(lineage)-317.7(2)-322(strains)-320.1(that)-320(had)-315.7(similar)]TJ
T*
[(neuroinvasive)-229.4(levels)-217.6(in)-221.9(mice)-215.3(to)-224.5(lineage)-216.5(1)-220.8(strains)-218.9(which)-219.9(caused)]TJ
0 -1.2267 TD
[(neurological)-530.5(disease)-526.9(in)-525.4(the)-528.6(United)-530.2(States)-524.9(were)-526.9(identied.)]TJ
28.0042 74.5598 TD
[(Similar)-202.9(genes)-198.6(were)-204.5(induced)-203.1(by)-198.5(highly)-199.7(neuroinvasive)-210.5(lineage)-197.5(1)]TJ
0 -1.2203 TD
[(and)-429.5(2)-435.8(strains,)-430.5(and)-435.9(increased)-434.2(expression)-433.6(of)-433.2(47)-435.3(genes)-432.5(in)-436.9(the)]TJ
0 -1.2266 TD
[(brain,)-318(111)-314.7(genes)-325.1(in)-316.7(the)-319.9(liver,)-321.1(and)-322(70)-315.2(genes)-318.7(in)-323.1(the)-319.9(spleen,)-322.1(rel-)]TJ
0 -1.2203 TD
[(ative)-484.7(to)-477.5(the)-484.3(3)-480.1(least)-485.3(neuroinvasive)-488.7(strains,)-481(were)-482.7(identied.)]TJ
T*
[(Genes)-534.4(involved)-542.4(in)-538(interferon)-540(signaling)-539.2(pathways,)-539.3(protein)]TJ
0 -1.2266 TD
[(degradation,)-636.4(T)-629(cell)-632.2(recruitment,)-642.5(major)-631.5(histocompatibility)]TJ
0 -1.2203 TD
[(complex)-423.9(class)-422.3(I)-425.7(and)-423.2(II)-421.5(antigen)-425.6(presentation,)-430.6(and)-423.2(apoptosis)]TJ
T*
[(were)-311.9(identied.)-319.8(These)-317.3(genes)-312.4(may)-311.3(have)-319.7(both)-314.5(pathogenic)-315.2(and)]TJ
0 -1.2266 TD
[(protective)-413.8(effects,)-409.4(but)-410.9(increased)-415.2(expression)-414.7(of)-407.9(certain)-411.4(acute)]TJ
0 -1.2203 TD
[(proteins,)-395.7(central)-398.8(nervous)-395.9(system-specic)-398.8(proteins,)-395.7(and)-397.9(pro-)]TJ
T*
[(teins)-406.9(associated)-402.6(with)-407.4(T)-401.3(cell)-404.6(hepatitis)-405.5(implicate)-407(mechanisms)]TJ
T*
[(related)-278.9(to)-281.4(exalted)-286.7(virulence)-284.2(\(Venter)-285.8(et)-278.6(al.)-277.9(2005\).)]TJ
/F3 1 Tf
0 -3.0603 TD
[(Genetic)-331.1(Determinants)-337.6(of)-336.6(the)-334.7(Virulence)]TJ
0 -1.2203 TD
[(of)-330.2(Lineage)-337.2(2)-333.2(Strains)]TJ
/F4 1 Tf
1.1128 -1.8336 TD
[(The)-322.4(complete)-320.9(genomes)-325.4(were)-324.6(sequenced)-322.3(for)-326.4(four)-321.4(lineage)-324(2)]TJ
-1.1128 -1.2203 TD
[(WNV)-273.7(strains)-282.1(isolated)-279.6(from)-273.4(patients)-281.8(in)-278.8(South)-278.3(Africa)-276.8(who)-279.7(had)]TJ
0 -1.2266 TD
[(mild)-330.1(or)-332.3(severe)-337.6(WNV)-330.6(infections.)-337.1(These)-336.3(strains)-332.7(had)-334.7(been)-330.1(pre-)]TJ
0 -1.2203 TD
[(viously)-251.6(shown)-252.8(to)-249.8(be)-250.9(highly)-250.3(or)-250.1(less)-252.7(neuroinvasive)-254.7(in)-253.5(mice)-246.9(and)]TJ
T*
[(induced)-392.8(genes)-388.3(similar)-389.1(to)-388.9(corresponding)-399.6(highly)-389.4(or)-389.2(less)-391.8(neu-)]TJ
T*
[(roinvasive)-288(lineage)-292.4(1)-290.4(strains)-288.4(in)-291.5(mice)-284.8(in)-291.5(the)-288.3(study)-295.1(described)-286.9(in)]TJ
0 -1.2266 TD
[(the)-364.2(previous)-365.8(paragraph.)-367.5(Phylogenetic)-367.8(and)-360(amino)-360.9(acid)-365.7(com-)]TJ
0 -1.2203 TD
[(parison)-467.8(of)-464.8(highly)-465.3(and)-461.2(less)-467.6(neuroinvasive)-469.7(lineage)-469.4(2)-461.1(strains)]TJ
T*
[(identied)-285.3(most)-286.6(variability)-283.1(in)-285.1(the)]TJ
/F9 1 Tf
14.4921 0 TD
(NS)Tj
/F4 1 Tf
1.606 0 TD
[(genes,)-290(especially)-281.8(the)-288.3(NS)]TJ
-16.0981 -1.2266 TD
[(protein)-296.6(5)-296.7(gene.)-301.4(All)-299.3(South)-297.3(African)-299.1(lineage)-305(2)-296.7(strains)-294.8(possessed)]TJ
0 -1.2203 TD
[(the)-244(envelope-protein)-251.7(glycosylation)-248.4(site)-245.5(previously)-247.2(postulated)]TJ
T*
[(to)-256.2(be)-250.9(associated)-257.2(with)-255.6(virulence)-258.9(\(Beasley)-258.6(et)-253.3(al.)-258.9(2005\),)-254.4(although)]TJ
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[(the)-180.8(prototype)-191.3(lineage)-178.6(2)-182.9(strain)-186(from)-184.9(Uganda)-182(\(B956D117B3\))-182(and)]TJ
0 -1.2203 TD
[(the)-193.4(nonneuroinvasive)-201(Madagascar)-195.3(strain)-192.3(AnMg798)-196.2(contained)]TJ
T*
[(deletions)-302.3(in)-304.1(the)-307.3(glycosylation)-305.3(site)-302.4(of)-300.4(the)]TJ
/F9 1 Tf
17.8369 0 TD
(E)Tj
/F4 1 Tf
.6007 0 TD
[(-protein)-309.8(relative)-305.5(to)]TJ
-18.4376 -1.2266 TD
[(the)-357.8(South)-360.5(African)-362.4(strains,)-360.9(which)-359(will)-360(prevent)-360.5(glycosylation.)]TJ
0 -1.2203 TD
[(Major)-228(deletions)-239.1(also)-228.4(existed)-231.6(in)-234.5(the)-231.4(3)]TJ
/F10 1 Tf
6.2762 0 0 6.2762 449.4613 378.3684 Tm
(0)Tj
/F4 1 Tf
8.9663 0 0 8.9663 453.7133 375.0802 Tm
[(noncoding)-234.6(region)-236(of)-230.9(two)]TJ
-15.9337 -1.2203 TD
[(of)-186.6(the)-187.1(lineage)-191.2(2)-182.9(strains)-193.6(that)-187.2(were)-185.5(previously)-190.3(shown)-189.5(to)-186.6(be)-187.7(either)]TJ
T*
[(less)-252.7(or)-250.1(not)-246.9(neuroinvasive)-254.7(relative)-254.9(to)-249.8(the)-250.3(highly)-256.6(neuroinvasive)]TJ
0 -1.2266 TD
[(strains)-282.1(sequenced)-284.3(in)-278.8(this)-286.9(study)-282.4(\(Botha)-281.5(et)-278.6(al.)-284.2(2008\).)]TJ
1.1128 -1.2203 TD
[(Although)-438(phenotypic)-437.2(investigations)-445.6(of)-433.2(mutations)-440.3(identi-)]TJ
-1.1128 -1.2203 TD
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[(described)-539.8(for)-541.4(lineage)-545.3(1)-537(strains.)-544.3(Lineage)-538.4(1)-543.3(viruses)-540(having)]TJ
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[(phenotypes)-600(of)-597.6(reduced)-595.2(virulence)-600.4(in)-595(mice)-594.6(and)-593.9(inefcient)]TJ
T*
[(growth)-639.3(in)-632.9(culture)-638.9(were)-640.7(identied)-639.4(in)-639.2(Mexico.)-635.3(Molecular)]TJ
0 -1.2266 TD
[(characterization)-464.4(of)-464.8(these)-466.5(isolates)-467.6(suggested)-465(that)-465.4(mutations)]TJ
0 -1.2203 TD
[(leading)-333.4(to)-332(loss)-337.7(of)]TJ
/F9 1 Tf
7.9732 0 TD
(E)Tj
/F4 1 Tf
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[(-protein)-335.1(glycosylation)-336.9(together)-334.5(with)-337.8(mu-)]TJ
-8.5802 -1.2203 TD
[(tations)-397.2(in)-392.6(the)]TJ
/F9 1 Tf
6.3545 0 TD
(NS)Tj
/F4 1 Tf
1.7135 0 TD
[(protein)-397.8(genes)-394.6(may)-393.5(be)-396.3(associated)-396.3(with)-394.7(at-)]TJ
-8.068 -1.2203 TD
[(tenuation)-242.4(\(Beasley)-239.7(et)-240.6(al.)-239.9(2005\).)-241.7(In)-239.5(another)-244.1(study,)-241.1(comparisons)]TJ
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[(between)-205.6(the)-206.1(prototype)-203.9(strain)-204.9(\(B956\))-204.8(and)-201.9(a)-201.8(variant)-203.9(obtained)-206.7(by)]TJ
0 -1.2203 TD
[(molecular)-299(mutation)-299.9(\(B956D117B3\))-302.1(revealed)-304.4(changes)-302(in)-297.8(the)]TJ
/F9 1 Tf
26.063 0 TD
(E)Tj
/F4 1 Tf
-26.063 -1.2203 TD
(and)Tj
/F9 1 Tf
1.998 0 TD
(NS)Tj
/F4 1 Tf
1.6503 0 TD
[(genes,)-328(which)-327.4(resulted)-326.3(in)-323.1(reduced)-329.6(virulence)-328.5(for)-326.4(mice)]TJ
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[(\(Yamshchikov)-431.6(et)-430.3(al.)-429.6(2004\).)-431.4(None)-429.7(of)-433.2(the)-427.4(attenuated)-437.9(isolates)]TJ
0 -1.2203 TD
[(could,)-196.2(however,)-208(be)-194(correlated)-205.8(with)-198.7(clinical)-199(disease)-204.5(in)-196.6(humans,)]TJ
T*
[(because)-347.1(they)-349.6(were)-349.9(either)-349.3(isolated)-349.1(from)-349.3(birds)-348.1(or)-344.9(modied)-347.9(in)]TJ
0 -1.2266 TD
[(culture.)-186.6(Substitution)-186(of)-186.6(the)-187.1(cysteine)-182.9(by)-185.9(serine)-185.8(at)-183.3(position)-189.9(102)-181.9(of)]TJ
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[(the)-256.7(NS4B)-260.2(by)-255.4(site-directed)-262.1(mutagenesis)-265.6(leads)-260.2(to)-256.2(the)-256.7(formation)]TJ
T*
[(of)-281.4(a)-284(4)0(1)]TJ
/F7 1 Tf
2.9275 0 TD
(8)Tj
/F4 1 Tf
.3857 0 TD
[(C)-284.7(temperature)-286.4(sensitive)-286(phenotype)-288.8(as)-285.4(well)-286.8(as)-279(attenu-)]TJ
-3.3132 -1.2266 TD
[(ation)-338.5(of)-332(the)-338.9(neuroinvasive)-343.2(and)-334.7(neurovirulent)-344.2(phenotypes)-340.7(in)]TJ
0 -1.2203 TD
[(mice)-240.6(\(Wicker)-235(et)-240.6(al.)-239.9(2006\).)-241.7(An)-238.7(adaptive)-235.7(mutation)-243(of)-243.5(Glu)-237.6(to)-237.2(Gly)]TJ
T*
[(at)-297.2(residue)-294.2(249)-295.7(\(E249G\))-298.4(in)-297.8(the)]TJ
/F9 1 Tf
13.0378 0 TD
(NS4B)Tj
/F4 1 Tf
2.7252 0 TD
[(gene)-292.1(resulted)-301(in)-297.8(reduced)]TJ
-15.763 -1.2203 TD
[(RNA)-378.7(synthesis)-379.4(in)-380(host)-381(cells)-374.3(\(Puig-Basagoiti)-383.8(et)-379.7(al.)-372.7(2007\).)-380.8(An)]TJ
0 -1.2266 TD
[(infectious)-218.3(clone)-217.5(of)-218.2(the)-218.7(NY99)-211.9(strain,)-220.5(which)-219.9(is)-213.5(highly)-218.7(virulent)-216(in)]TJ
0 -1.2203 TD
[(American)-315.1(crows,)-312.1(was)-318.6(compared)]TJ
/F9 1 Tf
14.5617 0 TD
[(in)-309.8(vitro)]TJ
/F4 1 Tf
3.3638 0 TD
[(with)-312.5(a)-315.7(Kenya)-313.5(strain)]TJ
-17.9255 -1.2203 TD
[(\(KEN-3829\))-391(that)-389.5(has)-389.9(reduced)-392.8(virulence)-398(in)-386.3(American)-391(crows.)]TJ
0 -1.2267 TD
[(The)-373(KEN-3829)-377.4(strain)-375.6(showed)-378.7(a)-372.6(6500-fold)-375(reduction)-381.1(in)-373.7(viral)]TJ
/F3 1 Tf
-28.0042 77.228 TD
[(WNV)-337.3(LINEAGE)-336.1(2)-333.2(PATHOGENESIS)]TJ
53.0113 0 TD
(661)Tj
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/F4 1 Tf
8.9663 0 0 8.9663 62.022 725.7825 Tm
0 0 0 rg
0 Tc
0 Tw
[(RNA)-391.3(production)-398(compared)-389.8(with)-394.7(a)-385.2(17-fold)-395(reduction)-393.8(in)-392.6(the)]TJ
0 -1.2203 TD
[(NY99)-294.1(strain)-293.4(at)-290.8(temperatures)]TJ
/F11 1 Tf
12.7533 0 TD
(>)Tj
/F4 1 Tf
.7714 0 TD
(44)Tj
/F7 1 Tf
.999 0 TD
(8)Tj
/F4 1 Tf
.3857 0 TD
[(C,)-293.9(suggesting)-296.4(that)-288.4(efcient)]TJ
-14.9094 -1.2266 TD
[(replication)-523.8(at)-518.5(high)-520.6(temperatures,)-524.5(as)-519.3(experienced)-525.2(in)-519.1(birds,)]TJ
0 -1.2203 TD
[(could)-439.9(be)-446.9(an)-439.2(important)-446(virulence)-442.3(factor)-445.8(of)-439.5(the)-440(NY99)-445.8(strain)]TJ
T*
[(\(Kinney)-283.5(et)-284.9(al.)-277.8(2006\).)]TJ
/F3 1 Tf
0 -3.0603 TD
[(Risk)-337.7(of)-330.2(Zoonotic)-335.5(and)-338.2(Laboratory)-336.5(Infections)]TJ
/F4 1 Tf
1.1128 -1.8336 TD
[(Two)-696.6(occupational)-706(zoonotic)-697.4(human)-700.7(WNV)-697.3(cases)-703.2(were)]TJ
-1.1128 -1.2203 TD
[(identied)-285.3(in)-285.1(South)-284.7(Africa,)-286(where)-283.7(patients)-281.8(were)-286.7(infected)-288.1(with)]TJ
T*
[(WNV)-431.8(lineage)-431.5(2)-429.5(strains,)-436.8(one)-429.7(laboratory)-436.1(infection)-434(by)-432.5(needle)]TJ
T*
[(stick)-299.9(injury)-296.5(and)-296.8(one)-296.9(in)-297.8(a)-296.7(veterinary)-297.8(student)-300.8(during)-294.6(exposure)]TJ
0 -1.2266 TD
[(to)-230.9(infected)-231.2(horse)-229.4(brain)-226.5(while)-233.3(performing)-229.8(an)-230.5(autopsy.)-229.1(The)-227.6(two)]TJ
0 -1.2203 TD
[(cases)-456.6(were)-451(used)-454.5(to)-458.5(investigate)-453.5(the)-452.7(pathogenic)-460.6(potential)-457.5(of)]TJ
T*
[(lineage)-286.1(2)-277.7(strains)-282.1(in)-278.8(otherwise)-285.5(healthy)-286.5(adults.)]TJ
1.1128 -1.2266 TD
[(A)-260.6(foal)-265.5(that)-269.4(had)-265.1(to)-262.5(be)-263.5(euthanized)-266.9(with)-268.3(neurological)-271.3(disease)]TJ
-1.1128 -1.2203 TD
[(was)-464(autopsied)-468.5(at)-461.6(the)-465.3(Onderstepoort)-475(Faculty)-461.9(of)-464.8(Veterinary)]TJ
T*
[(Science,)-550.5(University)-556.8(of)-547(Pretoria.)-555.6(The)-550.1(signs)-545.1(included)-554.4(fever,)]TJ
0 -1.2266 TD
[(Schiff-Sherrington)-299.1(signs)-292.2(\(exaggerated)-292.6(stretch)-290.1(reexes)-291.4(follow-)]TJ
0 -1.2203 TD
[(ing)-257.9(spinal)-265.6(cord)-258.7(lesions\),)-259.4(as)-260.1(well)-261.5(as)-253.7(a)-258.8(white)-261.8(blood)-263.1(cell)-259.2(count)-260.2(of)]TJ
T*
(32)Tj
/F10 1 Tf
.999 0 TD
()Tj
/F4 1 Tf
.7714 0 TD
(10)Tj
6.7246 0 0 5.9768 86.8535 510.5762 Tm
(9)Tj
8.9663 0 0 8.9663 88.2708 506.6077 Tm
[(/L)-372.7(\(normal)-381(range)-374.6(in)-380(horses)-382.4(5.512)]TJ
/F10 1 Tf
15.4532 0 TD
()Tj
/F4 1 Tf
.7714 0 TD
(10)Tj
6.7246 0 0 5.9768 242.7023 510.5762 Tm
(9)Tj
8.9663 0 0 8.9663 244.0629 506.6077 Tm
[(/L\).)-376.1(Although)]TJ
-20.3029 -1.2203 TD
[(it)-490.9(initially)-493.3(responded)-489.5(to)-490.1(treatment,)-498.5(the)-490.6(foal)-486.8(had)-492.8(a)-486.4(relapse)]TJ
0 -1.2266 TD
[(with)-325.2(neurological)-328.2(deterioration)-330.5(and)-322(rectal)-325.9(prolapse)-332.9(and)-322(was)]TJ
0 -1.2203 TD
[(euthanized.)-560.6(The)-550.1(autopsy)-555(was)-552.5(performed)-562.8(by)-552.6(a)-549.6(veterinary)]TJ
T*
[(pathologist)-232.2(and)-220.9(two)-226.2(students.)-229.1(The)-227.6(brain)-226.5(and)-220.9(spinal)-227.6(cord)-227.1(were)]TJ
0 -1.2266 TD
[(removed)-497.8(for)-490.8(histopathology,)-498.6(and)-492.8(a)-492.7(sample)-496.4(was)-495.6(taken)-494.5(for)]TJ
0 -1.2203 TD
[(bacteriological)-286.4(and)-284.1(virological)-289.9(investigations.)-290.4(The)-284.5(WNV)-286.4(was)]TJ
T*
[(identied)-203.1(by)-192.2(RT-PCR)-203.1(in)-196.6(the)-199.8(brain.)-197.8(Five)-192(days)-197.9(after)-203.4(the)-193.4(autopsy,)]TJ
0 -1.2266 TD
[(the)-490.6(veterinary)-487.5(student)-490.4(who)-488.3(removed)-485.1(the)-490.6(brain)-485.8(developed)]TJ
0 -1.2203 TD
[(fever,)-320.8(malaise,)-311.3(myalgia,)-318.9(neck)-316.8(stiffness,)-318.6(and)-315.7(severe)-318.6(headache.)]TJ
T*
[(A)-361.8(rash)-359(appeared)-359.3(2)-359.9(days)-356(later.)-361.1(Symptoms)-358(persisted)-365.6(for)]TJ
/F7 1 Tf
24.6657 0 TD
(*)Tj
/F4 1 Tf
.999 0 TD
(10)Tj
-25.6647 -1.2266 TD
[(days.)-270.4(The)-278.2(patient)-274.2(was)-268(treated)-275.8(symptomatically)-278.5(and)-271.5(with)-274.6(bed)]TJ
0 -1.2203 TD
[(rest.)-479.5(The)-474.2(WNV)-476(was)-476.7(isolated)-475.6(in)-474.8(mice)-474.5(from)-475.7(his)-476.1(serum)-475.1(and)]TJ
T*
[(conrmed)-306.8(by)-306(PCR.)-305.9(Sequencing)-308.9(and)-303.1(phylogenetic)-310.9(analysis)-307.4(of)]TJ
T*
[(part)-286.6(of)-281.5(the)-288.3(NS5)-282.5(gene)-285.8(of)-287.8(WNV)-286.4(obtained)-282.6(from)-286(the)-288.3(foals)-287.7(brain,)]TJ
0 -1.2266 TD
[(the)-231.4(mouse)-236.9(isolate)-232.3(as)-228.4(well)-236.2(as)-228.4(the)-231.4(students)-240.7(serum)-228.5(was)-236.4(identical)]TJ
0 -1.2203 TD
[(and)-353.7(conrmed)-351.1(to)-351(be)-352.1(lineage)-349.3(2)-353.6(i)0(n)-348.4(all)-348(cases.)-352(Although)-355.8(the)-351.5(vi-)]TJ
T*
[(remia)-317.4(in)-316.7(humans)-316.3(and)-322(horses)-319.2(is)-314.7(generally)-316.5(too)-322.2(low)-317.7(to)-313.1(support)]TJ
0 -1.2266 TD
[(infection)-326.6(of)-319.4(mosquitoes,)-328.2(the)-319.9(viral)-324.2(load)-318.6(may)-317.6(be)-326.8(high)-318.2(in)-323.1(nerve)]TJ
0 -1.2203 TD
[(tissues)-350.6(of)-351(fatal)-344.9(cases)-349.1(that)-345.3(test)-349.9(positive)-355.1(by)-344(RT-PCR)-348.6(or)-344.9(immu-)]TJ
T*
[(nohistochemistry)-312.7(despite)-300.3(serum)-304.3(being)-306.5(negative)-302.7(\(reviewed)-306.9(in)]TJ
0 -1.2266 TD
[(Jupp)-364.9(2001,)-361.4(Hayes)-365.5(and)-366.3(Gubler)-362.7(2006\).)-361.8(The)-366.7(invasive)-366.7(nature)-365.7(of)]TJ
0 -1.2203 TD
[(autopsy)-517(may)-513.7(pose)-517.5(a)-511.7(higher)-514.8(risk)-515.8(for)-516.1(infection)-516.2(by)-514.7(mucous)]TJ
T*
[(membrane.)-201.9(Gloves)-203(were)-204.5(the)-206.1(only)-203.8(protective)-205.1(gear)-200.5(worn)-204.5(during)]TJ
T*
[(the)-655(autopsy;)-652.7(however,)-650.6(following)-652(this)-653.6(incident,)-658(biosafety)]TJ
0 -1.2266 TD
[(measures)-279.8(have)-275.4(been)-279.5(improved)-275.1(to)-281.4(include)-273.2(gloves,)-281.2(masks,)-272.6(and)]TJ
0 -1.2203 TD
[(eye)-282.4(visor)-280.9(at)-278.2(the)-288.3(facility)-280.3(\(Venter)-285.8(et)-278.6(al.)-284.2(2010\).)]TJ
1.1128 -1.2203 TD
[(In)-283.7(the)-282(second)-287.9(case,)-281.1(laboratory-acquired)-290.2(WNV)-286.4(meningoen-)]TJ
-1.1128 -1.2267 TD
[(cephalitis)-799.9(occurred)-803.7(in)-797.3(a)-796.2(29-year-old)-797.8(immunocompetent)]TJ
0 -1.2203 TD
[(female)-342.3(scientist)-348.3(at)-341.4(the)-345.2(NICD)-338.8(after)-348.8(a)-341(needle)-338.4(stick)-344.1(injury)-347.1(with)]TJ
T*
[(neuroinviasive)-207.7(lineage)-203.9(2)-201.8(WNV)-204.2(strain,)-201.5(SPU93/01,)-207.5(as)-203.2(described)]TJ
0 -1.2266 TD
[(in)-386.3(Venter)-386.5(et)-386.1(al.)-385.3(\(2009a\).)-387.1(This)-384.3(strain)-388.3(was)-388.2(previously)-386.4(isolated)]TJ
0 -1.2203 TD
[(from)-431.5(a)-429.5(patient)-432.3(with)-432.6(nonfatal)-430.4(encephalitis)-436.4(\(Burt)-429.6(et)-430.3(al.)-429.6(2002,)]TJ
T*
[(Botha)-413.8(et)-405(al.)-410.6(2008\).)-412.4(As)-407.4(part)-413(of)-407.9(this)-413.4(investigation,)-415.6(blood)-408.5(was)]TJ
0 -1.2266 TD
[(taken)-406(on)-404.5(the)-408.4(day)-399(of)-407.9(infection)-408.8(and)-404.2(from)-406.2(the)-402.1(day)-405.3(symptoms)]TJ
0 -1.2203 TD
[(started)-308.9(to)-313.1(provide)-309.2(a)-309.3(rare)-310.6(opportunity)-313.4(to)-306.7(investigate)-314.4(cytokine)]TJ
T*
[(expression)-275.6(from)-267.1(infection)-269.6(to)-268.8(recovery.)-270.6(The)-271.8(patient)-267.9(developed)]TJ
T*
[(backache,)-297.2(neck)-304.2(stiffness,)-299.6(and)-303.1(malaise)-295.7(on)-297(day)-297.8(7)-296.7(postinfection;)]TJ
0 -1.2266 TD
[(rash,)-893(mild)-892.8(fever,)-896.2(and)-897.4(meningoencephalitis)-900.3(symptoms,)]TJ
0 -1.2203 TD
[(including)-227.8(severe)-223.7(headache)-222.9(and)-220.9(photophobia)-228.1(on)-227.5(day)-221.9(8;)-217.4(and)-220.9(on)]TJ
T*
[(day)-430.6(9,)-432.4(arthralgia)-438.9(as)-430.8(well)-432.2(as)-430.8(a)-435.8(tender)-437.3(spleen)-433(and)-435.9(liver)-432(was)]TJ
0 -1.2267 TD
[(reported.)-195.1(Symptoms)-193.6(continued)-194.1(for)-187.3(19)-188.7(days)-191.6(and)-189.3(were)-191.8(biphasic.)]TJ
27.9978 74.5598 TD
[(Although)-387.5(the)-376.8(patient)-388(recovered)-379.9(by)-381.9(day)-373.7(26,)-381.3(photosensitivity)]TJ
0 -1.2203 TD
[(persisted)-315(for)-307.4(several)-309.1(months.)-309(Due)-312.5(to)-306.7(the)-307.3(nature)-308.8(of)-313.1(her)-307.5(work,)]TJ
0 -1.2266 TD
[(the)-300.9(scientist)-297.7(had)-290.4(received)-297.8(Aventis)-301.6(Pasteur)-295.5(yellow)-294(fever)-298.9(virus)]TJ
0 -1.2203 TD
[(vaccine)-448.2(6)-435.8(months)-445.2(before)-444.4(the)-446.4(accident)-444.6(and)-435.9(had)-442.2(satisfactory)]TJ
T*
[(seroconversion)-326(yet)-320.9(was)-312.3(not)-322.8(protected)-317.7(from)-317.6(neurological)-321.9(dis-)]TJ
0 -1.2266 TD
[(ease.)-446.1(This)-441.2(contradicts)-443.7(the)-446.4(notion)-446.3(that)-440.1(yellow)-445.7(fever)-438(vaccine)]TJ
0 -1.2203 TD
[(may)-437.8(protect)-441.2(patients)-433.6(from)-437.8(WNV)-438.1(disease)-438.4(\(Tesh)-431.7(et)-436.6(al.)-435.9(2002,)]TJ
T*
[(Yamshchikov)-266.7(et)-253.3(al.)-258.9(2005\).)-254.4(The)-259.2(immunopathogenesis)-267.7(of)-256.2(WNV)]TJ
0 -1.2266 TD
[(was)-261.7(investigated)-266.8(by)-261.7(measuring)-258.3(16)-264.6(cytokines)-259.8(with)-261.9(pathogenic)]TJ
0 -1.2203 TD
[(and)-385.3(protective)-388.5(potential)-388(in)-380(the)-383.1(patients)-391.2(serum)-380.2(collected)-391(on)]TJ
T*
[(days)-412.9(0,)-413.4(8,)-413.4(9,)-413.4(10,)-406.6(11,)-412.9(13,)-412.9(16,)-412.9(and)-410.6(26)-410(postinfection.)-423.9(The)-411(most)]TJ
T*
[(signicant)-198.9(changes)-188.2(relative)-191.7(to)-192.9(a)-189.2(healthy)-191.6(control)-196.3(were)-185.5(noted)-192.9(for)]TJ
0 -1.2266 TD
(IFN)Tj
/F12 1 Tf
1.7135 0 TD
(a)Tj
/F4 1 Tf
.8346 0 TD
[(on)-341.3(days)-337(8,)-337.5(9,)-337.5(and)-334.7(13)-334.1(postinfection;)-348(IP10)-337.6(on)-341.3(day)-335.7(8;)-337.5(and)]TJ
-2.5481 -1.2203 TD
[(IL13,)-222(which)-219.9(was)-223.8(increased)-219.2(from)-222.8(day)-221.9(0)-214.5(t)0(o)-224.5(11.)-216.9(Proinammatory)]TJ
T*
[(cytokines)-386.2(IL6)-371.4(and)-378.9(IL8)-377.7(increased)-383.6(moderately)-378.5(on)-379.2(day)-373.7(16)-378.4(and)]TJ
0 -1.2266 TD
[(IL-15)-314.4(on)-303.3(day)-310.4(11.)-305.4(TNF)]TJ
/F12 1 Tf
9.4907 0 TD
(a)Tj
/F4 1 Tf
.8093 0 TD
[(and)-303.1(IL5)-308.1(increased)-314(slightly)-309.1(on)-309.7(day)-304.1(11,)]TJ
-10.3 -1.2203 TD
[(whereas)-196(no)-195.9(signicant)-192.6(change)-193.3(was)-192.1(noted)-192.9(for)-193.6(EOTAXIN,)-190.4(IFN)]TJ
/F12 1 Tf
25.9809 0 TD
(g)Tj
/F4 1 Tf
.4363 0 TD
(,)Tj
-26.4171 -1.2203 TD
(MIP1)Tj
/F12 1 Tf
2.3648 0 TD
(a)Tj
/F4 1 Tf
.4995 0 TD
[(,)-312.7(MIP1)]TJ
/F12 1 Tf
2.9275 0 TD
(b)Tj
/F4 1 Tf
.5501 0 TD
[(,)-312.7(RANTES,)-316.5(IL4,)-304.7(IL9,)-311(or)-313.3(IL10.)-310.6(The)-316.1(authors)-313(sug-)]TJ
-6.3419 -1.2266 TD
[(gested)-350.4(that)-351.6(the)-345.2(identied)-348.5(cytokines)-348.3(may)-349.3(serve)-344(as)-348.6(additional)]TJ
0 -1.2203 TD
[(targets)-215.4(for)-212.6(therapeutic)-218.5(interventions)-219.5(either)-210.2(by)-211.2(suppressing)-216(the)]TJ
T*
[(proinammatory)-497.8(response)-497.5(\(IL13,)-494.4(IL6,)-488.1(and)-492.8(IL8\))-492(or)-496.7(supple-)]TJ
T*
[(menting)-347.8(Th1)-347.3(type)-347.6(responses)-347.1(\(TNF)]TJ
/F12 1 Tf
15.2193 0 TD
(a)Tj
/F4 1 Tf
.8473 0 TD
[(and)-341(IFN)]TJ
/F12 1 Tf
3.7305 0 TD
(g)Tj
/F4 1 Tf
.4363 0 TD
[(\))-341.9(\(Venter)-349.1(et)-348.1(al.)]TJ
-20.2333 -1.2266 TD
[(2009a\).)-317.1(Improvement)-322.6(in)-316.7(mentation,)-317.4(speech,)-317.9(and)-315.7(eventual)-318.6(re-)]TJ
0 -1.2203 TD
[(covery)-267.1(was)-255.4(previously)-266.2(reported)-261.7(after)-266.6(experimental)-264.8(treatment)]TJ
T*
[(of)-559.7(2)-555.9(WNV)-558.2(patients)-560(with)-552.8(encephalitis)-562.9(and)-556(with)-559.1(synthetic)]TJ
0 -1.2266 TD
(IFN)Tj
/F12 1 Tf
1.7135 0 TD
(a)Tj
/F4 1 Tf
.4995 0 TD
[(2b)-269.5(\(Kalil)-272.6(et)-278.6(al.)-271.5(2005\).)-273.3(Data)-272.8(from)-273.4(this)-274.3(laboratory)-278(infection)]TJ
-2.213 -1.2203 TD
[(suggest)-487.4(that)-484.4(IFN)]TJ
/F12 1 Tf
7.714 0 TD
(a)Tj
/F4 1 Tf
.9864 0 TD
[(was)-483(also)-481.4(increased)-484.7(in)-481.1(this)-482.9(patient)-489.2(who)]TJ
-8.7003 -1.2203 TD
[(survived)-352.7(a)-353.6(neurological)-353.5(WNV)-349.6(infection)-351.8(and)-347.3(could)-351.4(therefore)]TJ
0 -1.2266 TD
[(be)-200.3(of)-192.9(benet.)-203.7(Both)-193(of)-199.3(these)-201(cases)-197.3(demonstrated)-195.4(the)-199.8(potential)-198.3(of)]TJ
0 -1.2203 TD
[(lineage)-349.3(2)-347.3(WNV)-349.6(strains)-351.7(to)-344.7(cause)-349.1(neurological)-353.5(disease)-349.9(in)-348.4(oth-)]TJ
T*
[(erwise)-285.2(healthy)-286.5(individuals.)]TJ
/F3 1 Tf
0 -2.447 TD
(Conclusion)Tj
/F4 1 Tf
1.1128 -1.8336 TD
[(It)-280.8(has)-276.1(been)-279.5(demonstrated)-277.6(that)-282(lineage)-279.7(2)-277.7(WNV)-273.7(strains)-282.1(exist)]TJ
-1.1128 -1.2203 TD
[(that)-383.2(are)-379.5(highly)-376.8(neuroinvasive)-381.2(and)-379(cause)-380.7(neurological)-378.8(infec-)]TJ
T*
[(tions)-258.1(of)-249.8(humans)-259.4(and)-252.5(animals)-248.6(in)-253.5(South)-253.1(Africa.)-254.4(Cases)-255.1(in)-253.5(horses)]TJ
0 -1.2266 TD
[(may)-349.3(have)-351.3(been)-355.4(missed)-348.1(in)-348.4(the)-351.5(past,)-353.3(because)-353.4(WNV)-349.6(transmis-)]TJ
0 -1.2203 TD
[(sion)-346.1(occurs)-346.1(at)-347.7(the)-345.2(same)-346.1(time)-342.9(as)-342.3(annual)-345.8(outbreaks)-343.7(of)-344.7(AHSV.)]TJ
T*
[(Increased)-812.1(awareness)-810.2(among)-810.7(veterinarians)-813.3(and)-808.9(medical)]TJ
0 -1.2266 TD
[(clinicians)-393.3(of)-388.9(the)-395.8(potential)-388(for)-389.6(WNV)-393.8(to)-388.9(cause)-387.1(severe)-394.5(disease)]TJ
0 -1.2203 TD
[(may)-324(lead)-328.4(to)-325.7(an)-319(increase)-330(in)-323.1(the)-326.2(number)-323.5(of)-325.7(cases)-323.8(detected)-328.4(an-)]TJ
T*
[(nually.)-353.8(Human)-343.2(cases)-349.1(of)-351(aseptic)-346.8(meningoencephalitis)-356.5(should)]TJ
0 -1.2267 TD
[(be)-187.7(screened)-184.4(to)-180.3(determine)-185.4(whether)-186.4(WNV)-178.9(cases)-184.7(can)-185.6(be)-181.4(detected.)]TJ
1.1128 -1.2203 TD
[(WNV)-242.1(may)-241.8(be)-238.3(under)-242.3(appreciated)-242.5(as)-241.1(a)-239.8(cause)-241.6(of)-237.2(neurological)]TJ
-1.1128 -1.2203 TD
[(disease)-274(in)-272.5(humans)-272.1(and)-271.5(horses)-275(in)-272.5(Southern)-276(Africa)-270.5(and)-271.5(should)]TJ
T*
[(be)-478.5(considered)-484.7(in)-474.8(humans)-480.7(and)-480.1(animals)-476.3(that)-478.1(develop)-485.4(acute)]TJ
0 -1.2266 TD
(meningoencephalitis.)Tj
/F3 1 Tf
0 -2.4406 TD
(Acknowledgments)Tj
/F4 1 Tf
1.1128 -1.8336 TD
[(This)-504.4(review)-499.6(summarizes)-501.8(the)-503.3(ndings)-502.6(of)-502.8(several)-498.8(papers)]TJ
-1.1128 -1.2266 TD
[(since)-443.7(2002.)-430.9(The)-436.2(authors)-439.5(thank)-441.1(the)-433.7(students)-441.2(and)-435.9(veterinary)]TJ
0 -1.2203 TD
[(pathologists)-486.4(at)-474.2(the)-478(University)-481(of)-477.5(Pretoria;)-479.8(scientists)-482.4(at)-474.2(the)]TJ
T*
[(Special)-631.6(Pathogens)-629.8(Unit,)-631.4(NICD;)-626.2(and)-625.5(veterinarians)-629.9(at)-625.9(the)]TJ
0 -1.2266 TD
[(Onderstepoort)-494(Veterinary)-489.5(Institute)-487.2(and)-486.4(in)-481.1(private)-486.8(practice)]TJ
0 -1.2203 TD
[(across)-194.6(South)-189.8(Africa)-188.3(who)-191.2(contributed)-196.3(to)-186.6(different)-195.2(aspects)-192.8(of)-186.6(the)]TJ
T*
[(work.)-315.9(The)-309.8(authors)-313(thank)-314.7(the)-313.6(National)-309.9(Research)-318(Foundation,)]TJ
T*
[(The)-575.3(Poliomyelitis)-572(Research)-577.3(foundation,)-573.7(and)-575(the)-566.5(National)]TJ
0 -1.2266 TD
[(Health)-322.9(Laboratory)-321.8(Services)-320(for)-320.1(funding.)-319.7(This)-314.7(work)-319.3(has)-320.3(been)]TJ
0 -1.2203 TD
[(cleared)-353.6(by)-350.3(the)-351.5(human)-353(ethics)-349.3(committee)-355.5(of)-344.7(the)-351.5(University)-354.5(of)]TJ
T*
[(Pretoria)-508.4(and)-499.1(the)-496.9(animal)-500.2(ethics)-507.4(committee)-501(of)-502.8(the)-496.9(National)]TJ
0 -1.2267 TD
[(Health)-285(Laboratory)-283.8(Services.)]TJ
/F3 1 Tf
-27.9978 77.2217 TD
(662)Tj
41.3455 0 TD
[(VENTER)-340.1(AND)-330.9(SWANEPOEL)]TJ
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