ICANCER RESEARCH (SUPPL.) 45, 4630s-4632s, September1985]
Antibodiesto HTLV-l p24 in Africanand PortuguesePopulations1
B. Larouze,2 L Schaffar-Deshayes, S. Blesonski, C. Gaudebout, J. M. Afoutou, P. Couillin, M. Da Graca Porto,
L Diakhate, M. L Frelut, M. Jeddi, E. Mrcier, F. Noireau, B. Nouasria, M. Ravaoarinoro, and J. P. Levy
lrsstltutde Módeclneat d'Epk*nlologle TrOPIC8I.S/INSERM
U13, H@tIta!Claude Bernard, 75944 ParIs COdex 19, France (B. L., C. G.J; INSEAMU152, HÔpIta!Coch!n,
75014 ParIs,France(L. S., S. B., J. P. L.J;INSEAMU73, Château
ciaLongchamps,75016 ParIs,France(P. C.]; [email protected]'sldade
do Po,fo,
Portuga!(M. D. G. P.]; Faculté
cia Médec!ne
ciaDakar, SónógaI(J.
M. A., L. D.J; HdpItaIde Bangui, CentraIAfrICWtRepublic (M. L. F.]; Facultóde Pharmaciedo Monastlr,
Tunisia(M. J.J; Equ!peMÔdICOJe
cia Tokora,Uganda(E. M.J; Officede Ia ReCherCI'*SCIOntIfIqUe
at TechniqueOutreMe, Brazzavile, the Congo(F. N.); Servicedo
pathologle infectleuse, HópltaIdo Constantine,Algeria (B. N.); Instltut Pasteurdo TananarWe,Madagascar (M. A.)
Allsaraweretestedforthe presenceof antibodies
againstp24,the
Abstract
major internal protein of HTLV-I as determined by a RIA deScrIbed
Usinga radloimmunoassay
to detectHTLV-Iprotelnantibodies
of molecularweight24,000, we screenedpopulations
fromA@
geria(140 subjects),Tunisia(442), Mali (69), Senegal(415),
Uganda(135),theCentralAfricanRepublic(77),theCongo(360),
andMadagascar
(193).Onlyfoursubjectswerepositive(1 from
Senegal,1 from Uganda,2 from the Congo).This is a much
lowerfigurethanthatfoundby othersinAfricabytheenzyme
linkedimmunosorbentassaytechnique.In addition,319 Portu
gueseblood donors(46 of whom have livedin Angolaor Moz
ambique)were screenedusingthe sameradioimmunoassay.
All
werenegative.
Introduction
previously
(13).
Sarawerescreened
at 1:5dilution.Saraprecspftating
morethan5%
of ‘@I-IabeIed
p24wereretestedat 1:2dilution.Saraprecipitating
more
than15% of labeledHTLV-lp24 wereconsidered
positiveand were
titered.
Seraprecipitating
lessthan5%wereconsidered
negative.
Sera
precipftating between 5 and 15% were considered doubtful. No doubtful
sara were found in the present Study. Serum titers were expressed by
thegreatest
dilution
whichprecipitated
atleast15%oflabeled
p24.
Results
Of the 1836 samplesfrom AfricanpopulatIons,four gave
positiveresults:1 from a Senegalesepregnantwoman(titer: 1/
640);1 froma Ugandanpatient(1/5,120);and2 fromCongolese
subjects (1/160, 1/10,240).
HTLV-I3was initiallyisolatedin the UnitedStatesof America
AllsamplesfromPortuguese
populations
werenegative.
froman adultpatientwithT-celIlymphoma(1). Infectionwith
HTLV-lisendemicinthesouthwest
ofJapan(2,3),theCaribbean
Islands(4, 5), and parts of SouthAmerica(4, 6), whereHTLV-I Discussion
is associated with aggressive aduit T-ceII cancers.
Galloet a!. (7) suggestedthatHTLV-lhadbeencarriedfrom
Africa to Japan by Portugueseseamenin the 16th century.
Indeed,HTLV-linfectionhas beendetectedin humanbeingsin
Nigeria(8) and Kenya(9) and in monkeysfrom Africa (9, 10).
Recently,Saxingeret a!. (11) and Biggarat a!. (12) conducted
The prevalencerateof HTLV-lantibodieswe reportin popu
lations from Africa is low compared to the figures published by
Saxingeret a!. (11) and Biggar et al. (12). In particular,these
authors reported a prevalence rate of 2.3% in Tunisian patients
withinflammatorybreastcarcinomaand6.3% inUgandanBurkitt
lymphomapatientsand healthycontrols.Thesedifferencesmay
to HTLV-I
Uganda, and South Africa. With the exception of one group of be relatedto thetechniqueusedto detectantibodies
black South African blood donors, antibodiesto HTLV-Iwere and/orto the type of populationscreened.
We usedAlAto detectantibodiesspecificto p24,the major
detectedin everypopulation;the prevalencerate rangedfrom 2
internal
proteinof HTLV-I,whereasSaxingerandGallo(14)used
to 10%.
an
ELISAmethodusingdisrupted
viralparticlesas antigen.
We reporttheresultsobtainedfrom8 Africancountriesusing
AlAto detectHTLV-lp24 antibodies.
In addition,we screened Duringthe courseof infectionwith HTLV-I,p24 antibodiesmight
blooddonorsfromPortugalto testthe hypothesis
thatHTLV-l appearlessoftenand/orpersistfora shorterlengthoftimethan
antibodiesto other viral proteins.As far as internalproteinsare
wasnotcarriedfromAfricato Portugalbyseamen.
extensive surveys using ELISA in Tunisia, Egypt, Ghana, Nigeria,
concerned, p24 seems to be more immunogenic than p19 and
much more than p15 (15). Antibodiesrecognizingthe viral en
Populations and Method
velope proteIns were detected in the sara of patients with adult
T-cellleukemiaby usinga membraneimmunofluorescence
test
(16). It hasbeenshownthatsomesarawerepositiveby ELISA
andnegativeby radioimmunoassay
(14). Thesesaramightcon
tamantibodiesto the envelopeglycoproteins.Anotherexplana
Mostofthegroups
hadhadblooddrawnforotherpurposes.
Inaddition,319Portuguese
blooddonors,predominantly
men,were tionofthedifferences
betweenAlAandELISAresultsisthatthe
tested, including 46 subjects who had lived in Angola and Mozambique.
ELISAtest mightdetect antibodiesto commonantigenicdeter
The population screened consisted of 1836 subjects from northern,
tropical, and equatorial Africa. The types of populations, age ranges
(most of them were young adults), and sex ratios are shown in Table 1.
I Presented
2 To
3 The
whom
at the
requests
abbreviations
HTLV
Symposium,
for
reprints
used
we:
should
HTLV-I,
December
6 and
7,
1984,
Bethesda,
MD.
be addressed.
-II,
and
-Ill,
human
T-lymphotropic
virus
types I, II, and III, respectively;RIA, radlommmunoassay;
p24, proteinwith a
molecularweightof24,000; other proteinsare sireilaslydesignated;EUSA, enzyme
linkedimmunosorbent
assay.
minants shared by some protelns of other types of HTLV. Those
determinants might not exist on HTLV-I p24. For example,
antibodiesagainst the envelopeglycoproteinsas detected by
membraneimmunofluorescence
were frequentlyfoundin sub
jects with the acquired immune deficiency syndrome (17),
whereas the lymphadenopathy-associated
virus LAV/HTLV-lIl
CANCERRESEARCH
VOL.45 SEPTEMBER
1985
4630s
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1985 American Association for Cancer Research.
HTLV-lp24 ANTIBODIES
IN AFRICAANDPORTUGAL
Theresultsobtainedin Portuguese
populations
do notseem
to supportthe hypothesis
that HTLV-lwas spreadfromAfrica
1
HTLV-ICountryPopulationAge
esults of radioimmunoassayscreenin for antibodiesto
Populationsand
rTable
p24 in Africag
positiveAlgeria
by Portugueseseamen.However,the populationtestedwas not
largeenoughto drawdefiniteconclusions.
(M:F)N°N°
rangeSexratio
Tunisia
Mali
Parturient women
Hospftal patients, immi
grantworkersin Paris
17-47
19-40
Senegal
Parturientwomen
Pregnantwomen
Patients from out-patient
dinics
CentralAfrican Hospital patients
Republic
Blood donors and general
Congo
population
Blood donors18-42
MadagascarProstitutes
Uganda
442
Acknowledgments
69
0
0
16—44
237
0
ThesamplesfromSenegalese
parturientswerecollectedby V. BarrelsandE.
Marinierduringa projecton maternaltransmbsionof hepatitisB viruscarriedout
15—50
1.04
20-40
178
135
1
1
in collaboration with the Institut de Medecine et Epidémiologie
Tropicales (Paris,
men
France)and the Divisionof ClinicalResearch,Institutefor CancerResearch,
Philadelphia,PA. We thank J. Mix for translating and typing the manuscript.
16-60
1.02
77
0
10-70
1.30
360
2
38—61All3.37140 1980
The unlabeledpurifiedp24 proteinwas kindlyprovidedby R. Galloand M.
Samgadharan.
0
References
1. Poiesz,B. J., Ruscetti,F. W., Gazdar, A. F., Bunn, P. A., Minna,J. D., and
hasbeenisolatedfromthe samepatients(18—20).
It shouldbe
pointedout that a highrate of LAV/HTLV-lIIseropositivity
in
healthyindividualshas been reported recentlyfrom Zaire (21).
Untilnow, suchcommonantigenicdeterminantsbetweenHTLV
I andHTLV-lIIhavenotbeenreported,whereastheyhavebeen
foundforsomeproteinsof HTLV-IandHTLV-II(22).
Interestingly
enough,whentestingtheseAfricanpatientsby
AlA, the backgroundwas low and similar to that which we
observed in European and Caribbean populations (5). This con
Gallo,R. C. DetectionandIsolationof typeC retrovirusparticlesfromfresh
andculturedlymphocytes
of a patientwithcutaneousT-celllymphoma.Proc.
Nat Aced. Sd. USA, 77: 7415—7419,
1980.
2. Hinuma,V., Komoda,H., Chose,T., Kondo,T., Kohakura,M., Takenaka,T.,
Kikuchi, M., Ichimary,M., Yunoki, K., Sato, I., Matsuo, R., Takiuchi, Y., Uchino,
H., and Hanaoka, M. Antibodiesto adult T@ceNleukemia-virus-associated
antigen (ATLA) in sara from patients with ATL and controls in Japan: a nation
wideseroepidemiologic
study.Int.J. Cancer,29:631—635,
1982.
3. Robert-Guroff,
M., Nakao,V., Notake,K.,Ito,V., Sliski,A.,andGallo,A. C.
Naturalantibodiesto humanretrovirusHTLVin a clusterof Japanesepatients
withadultT-ceNleukemia.Science(Wash.DC),215:975-978,1982.
4. Blattner,W. A., Kalyanaraman,V. S., RObert-GUrOff,
M., Uster, T. A., Galton,
D. A. G., Sam, R. S., Crawford,M. H., Catovsky,D.. Greaves,M., and Gallo.
R. C. The humantype-Cretrovirus,HTLV, inblacksfromthe Caribbeanregion
trastswiththehighbackground
observedwiththeELISAwhich
andrelationshipto adultT-cellleukemla/lymphoma.
Int.J. Cancer,30: 257264,1982.
mayberelatedto P!asmodiumfa!ciparuminfectionandattributed 5. Schaffar-Deshayes,L,
Chavance, M., Monplaislr, N., Couroucé,
A. M., Gas
to polyclonalhypergammaglobulinemia
(11, 12).
sam,A., Blesonsld,S., Valette,I., Feingold,N.,andLevy.J. P. Antibodiesto
HTLV-Ip24inseraofblooddonors,oldpeople,andpatientswithhaemopoietic
Giventhediversityof populations
screenedbyourselvesand
diseases in France and in the French West Indies. Int. J. Cancer, 34:667others,it is difficultto comparethe resultsdirectly.Several
671,1984.
F.A.,RUmke,R.,Robert-Guroff,
M.,Delange,
G.,andGallo,R.
populationsscreenedby Saxingeret a!. (11) in Africawere 6. Vyth-Dreese,
C. Antibodiesagainst human T-cell leukemia/lymphomavirus (HTLV) and
patientswithcancers.Thecharacteristics
of thosepopulations
expressionof HTLVp19 antigenIn relativesof a T.cell leukemiapatient
donotseemto accountforthehighprevalence
ratesobserved,
originatingfromSuilnam.Int.J. Cancer,32:337-342,1983.
C., Sliski,A., and WOn9-Staal,F. Originof humanT-ceIlIeukaemla
at leastinstudiesincluding
controlpopulations,
sincethefigures 7. GaIlo,R.
lymphomavirus.Lancet,2: 962—963.
1983.
weresimilarin bothcaseandcontrolgroups.Oneof the main 8. fleming,
A.,Yamamoto,
N.,Bhushurmath,
S.,Maharajan,
R.,Schneider,
J.,
characteristicsof the populationswe screened is that they
consistedof youngadultsand, in severalinstances,exclusively
women.No significant
sexdifferences
havebeenreporteduntil
nowfor HTLV-Iantibodies.
In termsof age,it shouldbe noted
that the highestprevalencerate observedby ELISA in popula
tionsfrom Ghana(12) was in the 11—29
agerange.
Thepossibility
of geographical
variations
shouldbetakeninto
andHunsman,G. Antibodiesto ATLV(HTLV)In Nigerianblooddonorsand
patients with chronic lymphocytic leukemiaor lymphoma. Lancet, 2: 334-335,
1983.
9. Hunsman,G., Schneider,J., Schmitt,J., andYamamoto,N. Detectionofserum
antibodiesto adultT-cellleukemiavirusin non-humanprimatesandpeople
fromAfrica.Int.J.Cancer,32:329-332,1983.
10. Yamamoto,N., Hinuma,V., Zur Hausen,H., Schneider,J., and Hunsmann,G.
African green monkeys are Infectedwith adult T-celIleukemiavirus or a closely
relatedagent.Lancet,1:240—241
, 1983.
11. Saxinger,W., Blattner,W. A., Levine,P. H., Clerk, J., Bigger,R., Hoh, M.,
Moghissi,J., Jacobs.P., W@son,
L, Jacobson,P., Crookes,A., Strong,M.,
Ansan,A. A., Dean,A. G.,Nkrumah,F., Mourali,N.,andGab, R. C. Human
account. The ELISA screenings (11, 12) showed marked varia
tions,including
absenceofantibodies,
inoneoftheSouthAfrican
populations.A low rate of HTLV-I antibodieshas been reported
previouslyin Kenyanstudents(9).
Ona worldscale,theHTLV-Ip24AlAdidnotdetectantibodies
in about 1000 sera from Frenchblooddonors(5).4However, in
blood donors from Martinique,a prevalencerate of 1.5% has
been found (5). It should be noted that most of the positive
T-celI leukemia virus (HTLV-l) antibodies in Africa. Science (Wash. DC), 225:
1473—1475,
1984.
12. Biggar,R. J., Saxinger,C., Gardiner,C., Collins,W. E., Levine,P. H., Clerk,
J. W., Nkrumah,F. K., and Blattner,W. A. Type-IHTLV antibodyIn urbanand
ruralGhana,WestAfrica.Int.J.Cancer,34:215-219,1984.
13. Kalyanaraman,V. S., Samgadharan,M. G., Nakao, Y., Ito, V., Add, T., and
Gallo,R. C. Natural antibodies to the structural core protein(p24)of the human
T-cellleukemia(lymphoma)retrovirusfoundin earsof leukemiapatientsin
Japan.Proc.Nat Aced.Sd., 79:1653-1657,1982.
subjectswere in the oldest age ranges. Negative resultshave
14. Saxinger,C. and Gallo,R. C. Applicationof the indirectenzyme-linkedin@mu
nosorbentassay microtestto the detectionand surveillanceof humanT.cell
beenobtainedby othersin Germany(9).
15. Schupbach,J., Kalyanaraman,V. S., Samgadharan,M. G., Nakao, V., Ito, V.,
Clearly, a better knowledge of the dynamics of antibodies is
required. Cross-sectional and longitudinal studies should be car
riedoutondifferenttypesofpopulations
indifferentplacesusing
varioustechniquesto assesstheirsensitivityand specificityand
leukemia-lymphoma
virus.Lab.Invest.,49: 371-377,1983.
andGallo,[email protected]'@ntitoimes
againstthreepurifiedstructuralproteinsof the
human type-C retrovirus, HTLV, in Japanese adult T-cellleukernla patients,
healthy family members, and [email protected]. J. Cancei, 32: 583—590,
1983.
16. Essex,M., McLane,M. F., and Lee, T. H. Antibodiesto humanT.celIleukemia
virusmembrane
antigens(HTLV-MA)inhemophillacs.
Science(Wash.DC),
alsothesignificance
of serological
profiles.
221:
1061—1063,
1983.
17. Essex,M., McLane,M. F., Lee, T. H., Falk,L, Howe, C. W. S., Cabradilla,C.,
4 L. Schaffar-Deshayes,
unpublished
and Francis,D. P. Antibodiesto cell membraneantigensassociatedwith
humanT.cellleukemia
virusinpatients
withAIDS.Science(Wash.DC),220:
data.
CANCERRESEARCHVOL. 45 SEPTEMBER1985
4631s
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1985 American Association for Cancer Research.
HTLV-I p24 ANTIBODIES
IN AFRICA AND PORTUGAL
20. Gallo,A. C., Salahuddin,
S. Z., Popovic,
M., Shearer,G. M., et a!. Frequent
859—862,
1983.
18. Barré-S@noussi,
F., Chermann,J. C., Ray, R., Nugeyre,M. T., Chamaret,S.,
Gruest,J., Dauguet,C., Axier-Blin,C., Vézinet-Brun,
F., Rouzioux,C., Roz
enbaum,W.,andMontagnier,L. Isolationof a T-lymphotropic
retrovirusfrom
a patient at risk for acquiredimmunedeficiencysyndrome(AIDS). Science
(Wash. DC), 220: 868—870,
1983.
19. Popovic,M., Samgadharan,M. G., Read, E., and Gallo, R. C. Detection,
isolation and continuous production of cytopathic retroviruses (HTLV-III)from
patientswithAIDSandpre-AIDS.Science(Wash.DC),224:497-@00,1984.
detection and isolation of cytopathic retroviruses (HTLV-III)from patients with
AIDS and at riskof AIDS. Science(Wash.DC), 224: 500—502,
1984.
21. Brun-Vesinet,F., Rouzioux,C., Montagnier,L., Chamarat,S., at al. Prevalence
of antibodiesto lymphadenopathy-associated
retrovirusin Africanpatients
with AIDS. Science (Wash. DC), 226: 4@3-456, 1984.
22. Samuel, K. P., Lautenberger, J. A., Jorcy, C. L, Josephs, S., at a!. Diagnostic
potentialfor human malignanciesof bacteriallyproducedHTLV-T envelope
protein. Science (Wash. DC), 226: 1094—1097,
1984.
CANCERRESEARCHVOL. 45 SEPTEMBER1985
4632s
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Antibodies to HTLV-I p24 in African and Portuguese Populations
B. Larouze, L. Schaffar-Deshayes, S. Blesonski, et al.
Cancer Res 1985;45:4630s-4632s.
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