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Journal ArticleDOI

Development and persistence of immunity to Epstein-Barr virus in man.

01 Nov 1970-The Journal of Infectious Diseases (Oxford University Press)-Vol. 122, Iss: 5, pp 401-409
TL;DR: EBV antibodies were shown to differ from lymphocytes from IM patients, and these results were confirmed by several laboratories but the interpretation has also been disputed.
Abstract: bodies to EBV was described by Henle et al. [2]; use of this technique for several recent studies showed that EBV is related to, or probably is the etiologic agent of infectious mononucleosis (IM). Henle et al. [3] reported that patients regularly develop antibodies to EBV during the course of IM. Diehl et al. [4] demonstrated EBV in acute phase lymphocytes from IM patients; these results were confirmed by several laboratories [5-11] but the interpretation has also been disputed [12-16]. EBV antibodies were shown to differ from the
Citations
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Journal ArticleDOI
TL;DR: Results obtained in a recent series of 90 patients with infectious mononucleosis are presented to show that an Epstein-Barr virus specific serodiagnosis can be established in most, if not all, cases, provided the most pertinent tests are performed.

500 citations

BookDOI
01 Jan 1979

481 citations

01 Jan 2012
TL;DR: PReVIously ClAssIfIed by IARC As “CARCInogenIC to humAns (gRoup 1)” And wAs deVeloped by sIx sepARAte woRkIng gRoups: phARmACeutICAls; bIologICAl Agents; ARsenIC, metAls, fIbRes, And dusts; RAdIAtIon; peRsonAl
Abstract: pReVIously ClAssIfIed by IARC As “CARCInogenIC to humAns (gRoup 1)” And wAs deVeloped by sIx sepARAte woRkIng gRoups: phARmACeutICAls; bIologICAl Agents; ARsenIC, metAls, fIbRes, And dusts; RAdIAtIon; peRsonAl hAbIts And IndooR CombustIons; ChemICAl Agents And RelAted oCCupAtIons. thIs Volume 100f CoVeRs ChemICAl Agents And RelAted oCCupAtIons, speCIfICAlly 4-AmInobIphenyl, benzIdIne, dyes metAbolIzed to benzIdIne, 4,4’-methylenebIs(2-ChloRoAnIlIne), 2-nAphthylAmIne, oRtho-toluIdIne, AuRAmIne And AuRAmIne pRoduCtIon, mAgentA And mAgentA pRoduCtIon, benzo[A]pyRene, CoAl gAsIfICAtIon, oCCupAtIonAl exposuRes duRIng CoAl-tAR dIstIllAtIon, CoAl-tAR pItCh, Coke pRoduCtIon, untReAted oR mIldly tReAted mIneRAl oIls, shAle oIls, soot, As found In oCCupAtIonAl exposuRe of ChImney-sweeps, oCCupAtIonAl exposuRes duRIng AlumInIum pRoduCtIon, AflAtoxIns, benzene, bIs(ChloRomethyl)etheR And ChloRomethyl methyl etheR, 1,3-butAdIene, 2,3,7,8-tetRAChloRodIbenzo-pARA-dIoxIn, 2,3,4,7,8-pentAChloRodIbenzofuRAn, And 3,3’,4,4’,5-pentAChloRobIphenyl, ethylene oxIde, foRmAldehyde, sulfuR mustARd, VInyl ChloRIde, IsopRopyl AlCohol mAnufACtuRe by the stRong-ACId pRoCess, mIsts fRom stRong InoRgAnIC ACIds, oCCupAtIonAl exposuRes duRIng IRon And steel foundIng, oCCupAtIonAl exposuRe As A pAInteR, oCCupAtIonAl exposuRes In the RubbeR mAnufACtuRIng IndustRy. beCAuse the sCope of Volume 100 Is so bRoAd, Its monogRAphs ARe foCused on key InfoRmAtIon. eACh monogRAph pResents A desCRIptIon of A CARCInogenIC Agent And how people ARe exposed, CRItICAl oVeRVIews of the epIdemIologICAl studIes And AnImAl CAnCeR bIoAssAys, And A ConCIse ReVIew of the Agent’s toxICokInetICs, plAusIble meChAnIsms of CARCInogenesIs, And potentIAlly susCeptIble populAtIons, And lIfe-stAges. detAIls of the desIgn And Results of IndIVIduAl epIdemIologICAl studIes And AnImAl CAnCeR bIoAssAys ARe summARIzed In tAbles. shoRt tAbles thAt hIghlIght key Results ARe pRInted In Volume 100, And moRe extensIVe tAbles thAt InClude All studIes AppeAR on the monogRAphs pRogRAmme websIte (http://monogRAphs.IARC.fR). It Is hoped thAt thIs Volume, by CompIlIng the knowledge ACCumulAted thRough seVeRAl deCAdes of CAnCeR ReseARCh, wIll stImulAte CAnCeR pReVentIon ACtIVItIes woRldwIde, And wIll be A VAlued ResouRCe foR futuRe ReseARCh to IdentIfy otheR Agents suspeCted of CAusIng CAnCeR In humAns. D es ig n by A ude la d es m ot s

378 citations


Cites background from "Development and persistence of immu..."

  • ...Many other epidemiological studies have shown since that EBV is highly prevalent throughout the world (IARC, 1997; Young, 2008), including in remote populations (Black et al., 1970; Tischendorf et al., 1970)....

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Journal ArticleDOI
TL;DR: It is evident that the virus must be considered in the diagnosis of various acute neurologic diseases affecting children and young adults, even in the absence of heterophil-antibody response or other signs of infectious mononucleosis.
Abstract: Infectious mononucleosis has been associated with Guillain--Barre syndrome, Bell's palsy, meningoencephalitis and transverse myelitis. Since it is not known that many children with infectious mononucleosis do not develop heterophil antibodies, we looked for evidence of current or recent Epstein-Barr virus infection in young patients with these neurologic diseases by using serodiagnostic procedures for detection and titration of antibodies to various antigens related to Epstein-Barr virus. Seven of 24 cases with Guillain-Barre syndrome and three of 16 with facial palsy were definitely associated with primary infection with Epstein-Barr virus as were two cases each of the other two neurologic diseases. Only one of these patients had obvious clinical infectious mononucleosis, and only a few demonstrated heterophil agglutinins. It is evident that the virus must be considered in the diagnosis of various acute neurologic diseases affecting children and young adults, even in the absence of heterophil-antibody response or other signs of infectious mononucleosis.

249 citations

Book ChapterDOI
01 Jan 1979
TL;DR: The detection of an apparently new virus in a specimen from a patient with a particular disease has to be followed by a series of immunologic and seroepidemiologic studies to determine whether the virus is truly new or can be identified with the aid of specific immune sera to known viruses.
Abstract: The detection of an apparently new virus in a specimen from a patient with a particular disease has to be followed by a series of immunologic and seroepidemiologic studies to determine (1) whether the virus is truly new or whether it can be identified with the aid of specific immune sera to known viruses; (2) whether the patient has or develops antibodies to the virus in the course of the disease; (3) whether other patients with the same disease also have antibodies to the new virus; (4) whether antibodies to the new virus are limited to patients with the given disease or whether they are also found in the general population which, in turn, would indicate whether infections by the new virus are invariably accompanied by signs of the disease or whether the disease is an unusual result of infection by the virus; and (5) if antibodies are found in healthy individuals, whether or not patients with the disease show higher titers and a broader spectrum of antibodies to virus-related antigens than individuals without clinical evidence of the disease. The value of these immunologic and seroepidemiologic approaches is well illustrated by the Epstein-Barr virus (EBV).

209 citations

References
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Journal ArticleDOI
TL;DR: Indirect immunofluorescence tests led to the brilliant staining of a small proportion of the cells in five different cultures derived from Burkitt's (African) lymphomas, and several observations suggest that the stainable cells might be those which are seen to harbor virus particles under the electron microscope.
Abstract: Henle, Gertrude (Children's Hospital of Philadelphia, Philadelphia, Pa.), and Werner Henle. Immunofluorescence in cells derived from Burkitt's lymphoma. J. Bacteriol. 91:1248-1256. 1966.-Indirect immunofluorescence tests led to the brilliant staining of a small proportion of the cells in five different cultures derived from Burkitt's (African) lymphomas. The reaction was not restricted to the 17 sera from cases of this disease but extended to many sera from American individuals, whether healthy donors or patients suffering from a variety of illnesses. The incidence of positive sera increased with age from about 30% in childhood to > 90% in adults. Fluorescein-isothiocyanate-conjugated human gamma-globulins were suitable for direct staining of the same proportion of cells. The stained cells appeared to be in varying stages of degeneration, but cultural conditions leading to an increase in the cellular death rates failed to result in a rise in fluorescent cells. Several observations suggest that the stainable cells might be those which are seen to harbor virus particles under the electron microscope. Two cell lines derived from leukemic patients in this country also contained a small fraction of stainable cells but two others, and numerous primary human leukocyte cultures, gave consistently negative results. Attempts to relate the staining to known viral antigens have failed to implicate herpes simplex, varicella, cytomegalo, and reo viruses types 1, 2, and 3. The nature of the virus carried by the lymphoma cells as well as of the staining reactions remains to be determined.

1,363 citations


"Development and persistence of immu..." refers methods in this paper

  • ...Serum antibodies to EBV were determined by the indirect fluorescent antibody method described by Henle and Henle [2]....

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  • ...[2]; use of this technique for several recent studies showed that EBV is related to, or probably is the etiologic agent of infectious mononucleosis (IM)....

    [...]

Journal ArticleDOI
TL;DR: It is indicated that EBV is related to, and probably the cause of, infectious mononucleosis, and that the agent has a world-wide dissemination.
Abstract: A herpes-type virus has been detected with remarkable frequency in cell lines derived from Burkitt's lymphomas, leukemic tissues, or buffy coats of a variety of patients and healthy donors.'-8 This agent is being named EB virus (EBV), for convenience, after the cell lines in which it was first observed.' M\\ost of the virus particles seen by electron microscopy in a small proportion of the cells are judged noninfectious because they are defective.\" 9. 10 To date, EBV has been transmissible only to cultured human cells of the hematopoietic system.\"'12 Virus-producing cells are readily detectable by indirect immunofluorescence tests with various human sera or by direct staining with fluorescein isothiocyanate-conjugated human y-globulins.'3'-7 Attempts to identify the agent by appropriate virus-specific immunofluorescence tests have failed. Thus EBV appears to be a new member of the herpes group.'3-\"5 From human serum surveys it is evident that infections by EBV, or a close relative of it, are frequent, and that the agent has a world-wide dissemination.\"3 117, 18 The age distribution of antibodies to EBV among American children parallels that of antibodies to other common viruses, such as measles, mumps, or poliomyelitis in the prevaccination era. 18 Except for the fact that all Burkitt's tumor patients studied thus far'3 1' and a high percentage of patients with carcinomas of the postnasal spaces'9 were found to have high titers of antibodies to EBV antigens, no other suggestive relationship of the virus to known disease entities has been recorded. The present report indicates that EBV is related to, and probably the cause of, infectious mononucleosis. Materials and Methods.-The techniques for growth and maintenance of cell lines derived from Burkitt's tumors have been described, as well as the procedures for preparation of cell smears, detection of EB virus antigens, and corresponding antibodies by immunofluorescence.3, 16 Cells of the EB-3 line were routinely used, which had been kept for 4-7 days on arginine-deficient Eagle's basal medium with 25% fetal calf serum (BME25) obtained by preincubation at 370C for 7 days or merely by omission of the amino acid. The arginine deficiency inhibits cellular growth but increases the number of EBV antigen-producing cells by a factor of 5-10 (to be published). Results.-The indirect immunofluorescence test for antibodies to EB virus was used in a search for illnesses that might be caused by this agent. In one series of tests, paired acute stage and convalescent sera from pediatric patients with unidentifiable viral infections were examined with negative results.18 As another approach, serial sera were tested that had been collected from children in prospective studies of viral infections. Such sets of sera were kindly supplied by Dr. John P. Fox from the \"New York Virus Watch,\" and by Dr. John H. Dingle from the Cleveland Family Study. Of the first group, 33 sets were examined that had been collected over periods of from one to four

1,128 citations


"Development and persistence of immu..." refers background in this paper

  • ...[3] reported that patients regularly develop antibodies to EBV during the course of IM....

    [...]

  • ...heterophile antibodies associated with IM and, unlike heterophile antibodies, to persist for years [3, 5, 6]....

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Journal ArticleDOI
15 Jan 1968-JAMA
TL;DR: Observations strongly indicate that EB virus, or a closely related one, is the etiologic agent of IM.
Abstract: In each of 29 patients with infectious mononucleosis (IM) the development of antibodies against a herpes-type virus (EB virus) has been demonstrated by an indirect immunofluorescence test with a virus bearing cell line (EB-3) derived from a Burkitt lymphoma. These antibodies, absent in pre-illness serum specimens, usually appeared early in the disease, rose to peak levels within a few weeks, and remained at relatively high levels during convalescence. They are clearly distinctive from heterophile antibodies and, unlike the latter, they persist for years, probably for life. Tests on sera from 50 randomly selected college freshmen revealed EB virus antibodies in 12, two of whom had positive histories of IM. Of 38 without demonstrable antibodies none had had IM, but the illness developed in three in the next two years. These and other observations strongly indicate that EB virus, or a closely related one, is the etiologic agent of IM.

387 citations


"Development and persistence of immu..." refers background or result in this paper

  • ...[4] demonstrated EBV in acute phase lymphocytes from IM patients; these results were confirmed by several laboratories [5-11] but the interpretation has also been disputed [12-16]....

    [...]

  • ...heterophile antibodies associated with IM and, unlike heterophile antibodies, to persist for years [3, 5, 6]....

    [...]

Journal ArticleDOI
TL;DR: In Yale students EBV antibody was always present in serum specimens obtained as long as eight years after clinical or subclinical infection, usually at levels of 1:40 or higher, and in a prospective study of 150 Yale students 53 hadEBV antibody on entry into college.
Abstract: The prevalence rate for antibody to EB virus measured by the indirect immunofluorescence technic in 1084 young adults varied from 26 to 87 per cent depending on age and geographic area. In a prospective study of 150 Yale students 53 had EBV antibody on entry into college; 43 of 97 students lacking antibody had seroconversion during the next four to eight years, 28 with recognized clinical infectious mononucleosis and 15 with inapparent or unrecognized illness. This was an infection rate of 11.1 per cent per year in the susceptible group. Of 164 Peace Corps volunteers 76 per cent had detectable anti-EBV titers on entrance into service, and of 30 lacking antibody 27 per cent were infected over one year while working in Colombia, South America. In Yale students EBV antibody was always present in serum specimens obtained as long as eight years after clinical or subclinical infection, usually at levels of 1:40 or higher.

274 citations


"Development and persistence of immu..." refers background in this paper

  • ...Seroepidemiologic surveys [6, 10, 11, 17-21] showed (7) a low incidence of EBV anti-...

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  • ...[21] in student populations (26-64 96 in the United States and 75-7796 in the PhUippines)....

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Journal ArticleDOI
TL;DR: In the case of the Epstein-Barr virus, it is no longer necessary to resort to the heterophile test as mentioned in this paper, since the virus has been identified and direct studies of infections due to this virus are possible.

254 citations


"Development and persistence of immu..." refers methods in this paper

  • ...Sera were screened for heterophile antibodies with the Monostat slide agglutination test (Colby, Chicago Heights, Illinois), and positive sera were then titrated for heterophile antibody titers [32]....

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