Following primary infection Epstein-Barr virus (EBV) establishes a persistent infection which is maintained for the life-time of the host. EBV can be found in a small number of circulating B cells, but the nature of the virus-cell interaction has not been fully established. Several assay systems are used to quantify persistent EBV infection, including PCR amplification of EBV DNA and spontaneous outgrowth of lymphoblastoid cell lines in culture. More recently, outgrowth of EBV-positive B cell tumours in severe combined immunodeficient (SCID) mice inoculated with peripheral blood mononuclear cells (PBMC) from normal EBV-seropositive donors has also been used to study B cell infection in vivo. In the present study we have compared the results of these two biological assay systems with PCR detection of EBV DNA and a regression assay as a measure of host T cell immunity to EBV. PBMC from ten normal EBV-seropositive donors were studied and although each test gave consistent results on repeat assays, no correlation was found between any of the assays tested. This result suggests that each assay measures a separate aspect of EBV persistence in B cells, and indicates a previously unrecognized degree of heterogeneity in the B cell population in which EBV resides.
AdldingerH. K.,
DeliusH.,
FreeseU. K.,
ClarkeJ.,
BornkammG. W.1985; A putative transforming gene of Jijoye virus differs from that of Epstein-Barr virus prototypes. Virology 141:221–234
BoyleT. J.,
TamburiniM.,
BerendK. R.,
KizilbashA. M.,
BorowitzM. J.,
LyerlyH. K.1992; Human B-cell lymphoma in severe combined immunodeficient mice after active infection with Epstein-Barr virus. Surgery 112:378–386
GopalM. R.,
ThomsonB. J.,
FoxJ.,
TedderR. S.,
HonessR. W.1990; Detection by PCR of HHV-6 and EBV DNA in blood and oropharynx of healthy adults and HIV-seropositives. Lancet 335:1598–1599
HendersonA.,
RipleyS.,
HellerM.,
KieffE.1983; Chromosome site for Epstein-Barr virus DNA in a Burkitt tumour cell line and in lymphocytes growth-transformed in vitro
. Proceedings of the National Academy of Sciences, USA 80:1987–1991
HoweJ. G.,
SteitzJ. A.1986; Localization of Epstein-Barr virus-encoded small RNAs by in situ hybridization. Proceedings of the National Academy of Sciences, USA 83:9006–9010
LewinN.,
AmanP.,
MasucciM. G.,
KleinE.,
KleinG.,
ObergB.,
StranderH.,
HenleW.,
HenleG.1987; Characterisation of EBV carrying B cell populations in healthy seropositive individuals with regard to density, release of transforming virus and spontaneous outgrowth. International Journal of Cancer 39:472–476
MiyashitaE. M.,
YangB.,
LamK. M. C.,
CrawfordD. H.,
Thorley-LawsonD. A.1995; A novel form of Epstein-Barr virus latency in normal B cells in vivo
. Cell 80:593–601
MosierD. E.,
GuliziaR. J.,
BairdS. M.,
WilsonD. B.1988; Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335:256–259
MossD. J.,
RickinsonA. B.,
PopeJ. H.1978; Long-term T-cell mediated immunity to Epstein-Barr virus in man. I. Complete regression of virus-induced transformation in cultures of seropositive donor leukocytes. International Journal of Cancer 22:662–668
MurrayR. J.,
KurillaM. G.,
BrooksJ. M.,
ThomasW. A.,
RoweM.,
KieffE.,
RickinsonA. B.1992; Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): implications for the immune control of EBV-positive malignancies. Journal of Experimental Medicine 176:157–168
NiedermanJ. C.,
EvansA. S.,
SubrahmanyanL.,
McCollumR. W.1970; Prevalence, incidence and persistence of EB virus antibodies in young adults. New England Journal of Medicine 282:361–365
PereraS. M.,
ThomasJ. A.,
BurkeM.,
CrawfordD. H.1998; Analysis of the T-cell micro-environment in Epstein-Barr virus-related post-transplantation B lymphoproliferative disease. Journal of Pathology 184:177–184
PicchioG. R.,
KobayashiR.,
KirvenM.,
BairdS. M.,
KippsT. J.,
MosierD. E.1992; Heterogenicity among Epstein-Barr virus- seropositive donors in the generation ofimmunoblastic B-cell lymphomas in scid mice receiving human peripheral blood leukocyte grafts. Cancer Research 52:2468–2477
PopeJ. H.,
HorneM. K.,
ScottW.1968; Transformation of foetal human leucocytes in vitro by filtrates of a human leukaemic cell line containing herpes-like virus. International Journal of Cancer 3:857–866
ReedmanB. M.,
KleinG.1973; Cellular localisation of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. International Journal of Cancer 11:499–520
RickinsonA. B.,
FinertyS.,
EpsteinM. A.1977; Comparative studies on adult donor lymphocytes infected by EB virus in vivo or in vitro : origin of transformed cells arising in co-cultures with foetal lymphocytes. International Journal of Cancer 19:775–782
RickinsonA. B.,
YoungL. S.,
RoweM.1987; Influence of the Epstein-Barr virus nuclear antigen EBNA2 on the growth phenotype of virus-transformed B cells. Journal of Virology 61:1310–1317
RoweM.,
YoungL. S.,
CrockerJ.,
StokesH.,
HendersonS.,
RickinsonA. B.1991; Epstein-Barr virus (EBV)-associated lympho-proliferative disease in the scid mouse model : implications for the pathogenesis of EBV-positive lymphomas in man. Journal of Experimental Medicine 173:147–158
ThomasJ. A.,
CrawfordD. H.,
BurkeM.1995; Clinicopathologic implications of Epstein-Barr virus-related B cell lymphoma in immuno-compromised patients. Journal of Clinical Pathology 48:287–290
VeroneseM. L.,
VeronesiA.,
D’AndreaE.,
Del MistroA.,
IndraccoloS.,
MazzaM. R.,
MionM.,
ZamarchiR.,
MeninC.,
PanozzoM.,
AmadoriA.,
Chieco-BianchiL.1992; Lymphoproliferative disease in human peripheral blood mononuclear cell-injected scid mice. I. T lymphocyte requirement for B cell tumour generation. Journal of Experimental Medicine 176:1763–1767
WhittleH. C.,
BrownJ.,
MarschK.,
GreenwoodB. M.,
SeidelinP.,
TigheH.,
WedderburnL.1984; T-cell control of Epstein-Barr virus-infected B cells is lost during P. falciparum malaria. Nature 312:449–450
YaoQ. Y.,
RickinsonA. B.,
EpsteinM. A.1985a; A re-examination of the Epstein-Barr virus carrier state in healthy seropositive individuals. International Journal of Cancer 35:35–42
YaoQ. Y.,
RickinsonA. B.,
GastonJ. S. H.,
EpsteinM. A.1985b; In vitro analysis of the Epstein-Barr virus : host balance in long-term renal allograft recipients. International Journal of Cancer 35:43–49