EBV has been declared a Class I human carcinogen by the IARC. (Epstein Barr Virus and Kaposi's Sarcoma Herpesvirus/Human Herpesvirus 8. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans). IARC Monograph 70. Lyon: International Agency for Research on Cancer; 1997.)
"5.5 Evaluation. There is sufficient evidence for the carcinogenicity of EBV in the causation of Burkitt's lymphoma, sinonasal angiocentric T-cell lymphoma, immunosuppression-related lymphoma, Hodgkin's disease and nasopharyngeal carcinoma."
"EBV is carcinogenic to humans (Group I)."
IARC Monograph 70, Epstein-Barr Virus, summary (1997) / IARC (pdf, 10 pp)Epstein-Barr virus, infectious mononucleosis, Burkitt's lymphoma and nasopharyngeal carcinoma. G Klein. Israel J Med Sci 1977 Jul;13(7):716-724. "The timing and extent of seroconversion are strongly related to socioeconomic status. In low socioeconomic groups, infection occurs during early childhood, as a rule. It is not accompanied by any recognized disease, and the route of transmission is unknown. Only a minority of children become infected in high socioeconomic groups where a later infection, during the teens, predominates."
Klein - Israel J Med Sci 1977 full article / tobacco documentThe spectrum of Epstein-Barr virus-associated lymphoproliferative
disease in Korea: incidence of disease entities by age groups. EY Cho,
KH Kim, WS Kim, KH Yoo, HH Koo, YH Ko. J Korean Med Sci 2008
Apr;23(2):185-192. "T or NK cell NHLs were the most common forms of
EBV-positive NHLs (107/167, 64%); among these, nasal-type NK/T cell
lymphomas were the most common (89/107, 83%). According to the age,
Burkitt's lymphoma was the most common in early childhood; in
teenagers, chronic (active) EBV infection-associated LPD was the most
common type. The incidence of NK/T cell lymphoma began to increase from
the twenties and formed the major type of EBV-associated tumor
throughout life. Diffuse large B cell lymphoma formed the major type in
the sixties and seventies."
Epstein-Barr virus and Hodgkin's disease. H Herbst, G Niedobitek.
Int J Clin Lab Res 1993;23(1):13-16. "Seroepidemiological and molecular
biological studies have established an association of Hodgkin's disease
with Epstein-Barr virus. Recently, Epstein-Barr virus genomes and gene
products have been detected in the neoplastic cells of approximately
50% of cases, most notably the latent membrane protein, which has
transforming potential."
Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents. FE Alexander, RF Jarrett, D Lawrence, AA Armstrong, J Freeland, DA Gokhale, E Kane, GM Taylor, DH Wright, RA Cartwright. Br J Cancer 2000 Mar;82(5):1117-1121. 19/103 tumors were EBV+. History of infectious mononucleosis & Hodgkin's disease, OR= 2.43 (95% CI= 1.10-5.33); history of IM and EBV-positive HD, OR= 9.16 (95% CI= 1.07-78.31).
Alexander - Br J Cancer 2000 abstract / PubMedThe correlation of Epstein-Barr virus expression and lymphocyte
subsets with the clinical presentation of nodular sclerosing Hodgkin
disease. A Kandil, S Bazarbashi, WA Mourad. Cancer 2001 Jun
1;91(11):1957-1963. EBV expression was seen in 24 (50%) cases.
South Asian ethnicity and material deprivation increase the risk of Epstein-Barr virus infection in childhood Hodgkin's disease. KJ Flavell, JP Biddulph, JE Powell, SE Parkes, D Redfern, M Weinreb, P Nelson, JR Mann, LS Young, PG Murray. Br J Cancer 2001 Aug;85(3):350-356. "62% of [55] cases were Epstein-Barr virus-positive... The relative risk of Epstein-Barr virus-positivity showed a gradient with increasing Townsend score; the risk being 7-times higher in the most deprived quartile compared with the least deprived group."
Flavell - Br J Cancer 2001 abstract / PubMedEpstein-Barr virus (EBV) in Chinese pediatric Hodgkin disease: Hodgkin disease in young children is an EBV-related lymphoma. XG Zhou, K Sandvej, PJ Li, XL Ji, QH Yan, XP Zhang, JP Da, SJ Hamilton-Dutoit. Cancer 2001 Sep 15;92(6):1621-1631. In 104 pediatric and 52 adult Chinese HD cases, "EBV was identified in tumor cells in 113 of 156 (72%) HD cases but was more frequent in pediatric cases (93 of 104; 89%) compared with adult cases (20 of 52; 38%) (P < 0.01; chi-square test). EBV was found in 86 out of 91 (95%) cases in children aged 3-10 years and in 7 out of 13 (54%) cases in children aged 11-14 years (P < 0.01; chi-square test).... The authors believe that pediatric HD now should be regarded as a distinctive EBV-related lymphoma."
Zhou - Cancer 2001 abstract / PubMedA defective, rearranged Epstein-Barr virus genome in EBER-negative
and EBER-positive Hodgkin's disease. YJ Gan, BI Razzouk, T Su, JW
Sixbey. Am J Pathol 2002 Mar;160(3):781-786. "The Epstein-Barr virus
(EBV) has been linked to approximately half the cases of Hodgkin’s
disease (HD), with virus localized by EBER in situ hybridization to the
malignant Reed-Sternberg cell that characteristically makes up less
than 1% of the tumor mass. Recent descriptions of relapsed HD, shown to
be EBV-positive at initial diagnosis but EBV-negative on reoccurrence,
raise the possibility of viral DNA loss during tumor progression in
some individuals." 8/24 EBER-negative HD had PCR evidence of defective
EBV DNA. "Detection of defective EBV genomes with the potential to
disrupt viral gene regulation suggests one mechanism for pathogenic
diversity that may also account for loss of prototypic EBV from
individual tumor cells."
Epstein-Barr virus in Hodgkin's disease: the example of central Tunisia. S Korbi, M Trimeche, B Sriha, MT Yacoubi, S Hmissa, M Mokni, P Delvenne, J Boniver, S Rammeh. Ann Pathol 2002 Apr;22(2):96-101. EBV early RNA transcripts (EBER) was detected in 70% of 77 cases.
Korbi - Ann Pathol 2002 abstract / PubMedHematopoietic and lymphatic cancers in relatives of patients with infectious mononucleosis. H Hjalgrim, K Rostgaard, J Askling, M Madsen, HH Storm, CS Rabkin, M Melbye. J Natl Cancer Inst 2002 May 1;94(9):678-681. "The unremarkable risk for Hodgkin's lymphoma in family members of patients with EBV-related infectious mononucleosis indicates that socioeconomic confounding is an unlikely explanation for the association between EBV-related infectious mononucleosis and Hodgkin's lymphoma."
Hjalgrim - JNCI 2002 abstract / PubMedEpstein-barr virus-associated non-Hodgkin's lymphoma of B-cell
origin, Hodgkin's disease, acute leukemia, and systemic lupus
erythematosus: a serologic and molecular analysis. W Mitarnun, J
Pradutkanchana, S Takao, V Saechan, S Suwiwat, T Ishida. J Med Assoc
Thai. 2002 May;85(5):552-9. In 58 patients, "EBV internal repeat-1
region (IR-1) in peripheral blood CD3+ cells was detected in 10 of 14
patients (71.5%) with NHL-B, 3 of 8 patients (37.5%) with Hodgkin's
disease, 1 of 6 patients (16.7%) with acute leukemia, 4 of 9 patients
(44.5%) with SLE, and was not detected in any of the 21 patients with
other diseases."
Hodgkin disease in adult and juvenile groups from two different geographic regions in Brazil: characterization of clinicopathologic aspects and relationship with Epstein-Barr virus infection. E De Oliveira, MM Bacchi, ES Abreu, L Niero-Melo, CE Bacchi. Am J Clin Pathol 2002 Jul;118(1):25-30. "HD in Brazilian patients is highly associated with EBV infection."
de Oliveira - Am J Clin Pathol 2002 abstract / PubMedHeterogeneity of risk factors and antibody profiles in epstein-barr
virus genome-positive and -negative hodgkin lymphoma.
ET Chang, T Zheng, ET Lennette, EG Weir, M Borowitz, RB Mann, D
Spiegelman, NE Mueller. J Infect Dis 2004 Jun 15;189(12):2271-2281.
"EBV-positive patients were less educated and more likely to have
smoked cigarettes and had more prevalent and higher EBV antibody
titers, compared with EBV-negative patients."
Phenotype and frequency of Epstein-Barr virus-infected cells in
pretreatment blood samples from patients with Hodgkin lymphoma. G Khan,
A Lake, L Shield, J Freeland, L Andrew, FE Alexander, R Jackson, PR
Taylor, EA McCruden, RF Jarrett. Br J Haematol 2005 May;129(4):511-519.
"[T]he frequency of circulating EBV-infected cells was significantly
higher (P < 0.001) in pretreatment blood samples from EBV-associated
cases when compared with non-EBV-associated cases."
HLA-A*02 is associated with a reduced risk and HLA-A*01 with an
increased risk of developing EBV+ Hodgkin lymphoma. M Niens, RF
Jarrett, B Hepkema, IM Nolte, A Diepstra, M Platteel, N Kouprie, CP
Delury, A Gallagher, L Visser, S Poppema, GJ te Meerman, A van den
Berg. Blood 2007 Nov 1;110(9):3310-3315. 70 patients with EBV+ HL, 31
patients with EBV- HL, and 59 control participants. "HLA-A*01 was
significantly overrepresented and HLA-A*02 was significantly
underrepresented in patients with EBV+ HL versus controls and patients
with EBV- HL. In addition, HLA-A*02 status was determined by
immunohistochemistry or HLA-A*02-specific polymerase chain reaction
(PCR) on 152 patients with EBV+ HL and 322 patients with EBV- HL. The
percentage of HLA-A*02+ patients in the EBV+ HL group (35.5%) was
significantly lower than in 6107 general control participants (53.0%)
and the EBV- HL group (50.9%)."
Expression of Epstein-Barr virus in Hodgkin lymphoma in a population
of United Arab Emirates nationals. S Al-Salam, A John, S Daoud, SM
Chong, A Castella. Leuk Lymphoma 2008 Jul 25:1-9. "Nodular sclerosis
(NS) subtype was the most common type of HL among UAE nationals
followed by mixed cellularity (MC), lymphocytic predominant (LP),
unclassified, lymphocytic depletion (LD) and lymphocyte rich (LR)
subtypes, respectively. EBV was seen in 17 of 45 (38%) cases of HL and
was predominately seen in the MC subtype followed by NS, LD and LR
subtypes, respectively. EBV was more frequently expressed in HL in the
pediatric age group than the adult age group."
Cigarette smoking and risk of Hodgkin's Disease: A population-based case-control study. NC Briggs, HI Hall, EA Brann, CJ Moriarty, RS Levine. Am J Epidemiol 2002;156(11):1011-1020. "Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals adjusted for age, registry, race/ethnicity, Jewish upbringing, education, and childhood domicile. Compared with never smokers, current smokers had a significantly increased risk of Hodgkin’s disease (odds ratio (OR) = 1.8, 95% confidence interval (CI): 1.3, 2.9)." They simply ignored EBV infection! This is an example of deliberate anti-smoker scientific fraud, under the auspices of the Centers for Disease Control, and published by the coruupt Johns Hopkins Bloomberg School of Public Health. In the year 2002, when no one can legitimately pretend ignorance, they purposely ignore the role of EBV infection, in order to falsely blame by confounding.
Briggs / Am J Epidemiol 2002 abstractThe National Cancer Institute claims that "At this time, the cause or causes of Hodgkin's disease are not known," and insists on calling EBV merely a "risk factor:" "Viruses -- Epstein-Barr virus is an infectious agent that may be associated with an increased chance of getting Hodgkin's disease." They refuse to admit that EBV is CAUSAL, and not merely associated with an increased chance of getting Hodgkin disease. (Risk Factors Associated with Hodgkin's Disease. National Cancer Institute. Posted 06/25/1999, Updated 09/16/2002; viewed 11-30-02, 06-18-05, 10-02-05, and 07-01-06.)
Risk Factors Associated with Hodgkin's Disease / National Cancer InstituteThe American Cancer Society mirrors the attitude of the NCI in its
evasion of the causal role of EBV. "There seems to be a slightly
increased rate for Hodgkin's disease
in people who have had infectious mononucleosis (sometimes
called "mono" for short), an infection caused by the Epstein-Barr
virus. However, half of patients with Hodgkin's disease show no
evidence of a previous Epstein-Barr virus infection." And they insist
that "Even if someone has one or more risk factors for Hodgkin's
disease, it is impossible to know for sure how much that risk factor
could contribute to causing the cancer. In general, we can say that no
major risk factors for Hodgkin's disease have been discovered yet."
(What Are the
Risk Factors for Hodgkin's Disease? American Cancer Society, as of
10-02-05 and 07-01-06.)
Precipitating antibody in human serum to an antigen present in
cultured Burkitt's lymphoma cells. LJ Old, EA Boyse, HF Oettgen, ED
Harven, G Geering, B Williamson, P Clifford. Proc Natl Acad Sci U S A
1966 Dec;56(6):1699-1704. 19 of 20 (95%) sera of patients with
carcinoma of the postnasal space were positive to an antigen prepared
from cultured Burkitt's lymphoma cells.
A Burkitt lymphoma cell line with integrated Epstein-Barr virus at a
stable chromosome modification site. NC Popescu, MC Chen, S Simpson, S
Solinas, JA DiPaolo. Virology 1993 Jul;195(1):248-251. "Virus insertion
into chromosomal DNA caused a stable modification site expressed as a
distinctive achromatic region adjacent to the band 2p13. The chromatid
lesion at the site of EBV integration involving a recombinogenic and
fragile site may have contributed to the development of the NAB-2 BL."
The role of Epstein-Barr virus-encoded small RNAs (EBERs) in oncogenesis. A Nanbo, K Takada. Rev Med Virol 2002 Sep-Oct;12(5):321-326. "EBERs play a key role in the maintenance of malignant phenotypes of Burkitt's lymphoma (BL) cells... Furthermore, we demonstrated that EBERs confer resistance to interferon (IFN)-alpha-induced apoptosis by inhibition of double-stranded (ds) RNA-activated protein kinase (PKR), which is the key mediator of the antiviral effect of IFN-alpha. These studies provide a new notion that RNA molecules contribute to oncogenesis."
Nanbo - Rev Med Virol 2002 abstract / PubMedFrequent presence of subtype A virus in Epstein-Barr virus-associated malignancies. SC Peh, LH Kim, S Poppema. Pathology 2002 Oct;34(5):446-450. In 17 Hodgkin's, 14 Burkitt's, 4 T-cell and 3 B-cell non-Hodgkin's lymphomas, "All cases showed presence of type A virus, consistently detected with nested PCR protocol but not with single step PCR. There was no type B virus or mix infections detected."
Peh - Pathology 2002 abstract / PubMedSporadic paediatric and adult Burkitt lymphomas share similar
phenotypic and genotypic features. SS Chuang, WT Huang, PP Hsieh, YC
Jung, H Ye, MQ Du, CL Lu, CY Cho, SC Hsiao, YH Hsu, KJ Lin.
Histopathology 2008 Mar;52(4):427-435. In 17 paediatric and 14 adult
BLs, 24% versus 21% were positive for EBER.
Detection of Epstein-Barr virus in children and adolescents with
Burkitt's lymphoma by in situ hybridization using tissue microarrays. M
Pizza, P Bruniera, SM Luporini, HR Marcelino da Silva, ML Borsato, HC
de Castro, FA Soares, RA Paes. Hematology 2008 Apr;13(2):114-118. "The
presence of EBV using in situ hybridization was found in 33/50 (66%)
and there was no association between the presence of the virus in the
tumor cells or patient age, as well as the survival rate."
Viral Studies in Burkitt Lymphoma: Association With Epstein-Barr
Virus but Not HHV-8. EM Queiroga, G Gualco, L Chioato, WJ Harrington, I
Araujo, LM Weiss, CE Bacchi. Am J Clin Pathol 2008 Aug;130(2):186-192.
"EBV was present in 45.0% of all BL cases with higher incidence in the
pediatric group; most cases were EBV type A. We found no association of
BL with HHV-8 in EBV + BL or in EBV-cases, including the HIV + BL
group." Number of cases is not given in the abstract.
[Detection of Epstein-Barr virus nucleic acid sequences in
non-Hodgkin's lymphoma]. A Sauerbrei, P Wutzler, I Farber, K Wutke, B
Brichacek, I Hirsch. Arch Geschwulstforsch 1987;57(6):445-452. EBV
nucleic acid and EBNA were found in 5/25 NHLs.
Epstein-Barr virus-associated peripheral T-cell lymphoma of
activated CD8 phenotype. IJ Su, KH Lin, CJ Chen, HF Tien, HC Hsieh, DT
Lin, JY Chen. Cancer 1990 Dec 15;66(12):2557-2562. Two childhood cases.
Frequent latent Epstein-Barr virus infection of neoplastic T cells
and bystander B cells in human immunodeficiency virus-negative European
peripheral pleomorphic T-cell lymphomas. P Korbjuhn, I Anagnostopoulos,
M Hummel, M Tiemann, F Dallenbach, MR Parwaresch, H Stein. Blood 1993
Jul 1;82(1):217-223. 38 of 81 cases (47%) of PMTCL were positive for
EBER by ISH. "By EBER-ISH, the virus was located in the tumor cells in
30 of the 38 EBV-positive cases, with the proportion of the infected
cells ranging from 1% to 100%. In 18 of these cases and in the 8 cases
without EBV-infected tumor cells, the virus was, respectively, either
additionally or exclusively detectable in occasional nonmalignant
lymphoid bystander cells."
Sinonasal T-cell lymphoma in the differential diagnosis of lethal midline granuloma using in situ hybridization for Epstein-Barr virus RNA. M Dictor, A Cervin, O Kalm, E Rambech. Mod Pathol 1996 Jan;9(1):7-14.
Dictor - Mod Pathol 1996 abstract / PubMed[Two cases of lethal midline granuloma thought to be of natural killer cell origin]. S Tamura, N Yamanaka, T Saito, I Takano, M Hotomi, M Yokoyama. Nippon Jibiinkoka Gakkai Kaiho 1996 Jan;99(1):46-53.
Tamura - Nippon Jibiinkoka Gakkai Kaiho 1996 abstract / PubMedEpstein-Barr virus in T and natural killer (NK) cell non-Hodgkin's lymphomas. P Kanavaros, J Briere, JF Emile, P Gaulard. Leukemia 1996 Jun;10 Suppl 2:s84-s87. Review.
Kanavaros - Leukemia 1996 abstract / PubMed[Epstein-Barr virus infection in midline malignant reticulosis]. W Liu, J van Gorp, G Li. Zhonghua Zhong, Liu, Za Zhi 1997 Jan;19(1):49-52.
Liu - Zhonghua Zhong Liu Za Zhi 1997 abstract / PubMed[Clinical characteristics of Epstein-Barr virus-associated natural killer cell lymphoma/leukemia]. K Kawa. Nippon Rinsho 1997 Feb;55(2):424-428.
Kawa - Nippon Rinsho 1997 abstract / PubMedNatural killer cell lymphoma/leukemia: pathology and treatment. YL Kwong, AC Chan, RH Liang. Hematol Oncol 1997 May;15(2):71-79. Review. "A consistent association with monoclonal Epstein-Barr virus infection in the tumour cell has been observed... Clinically, most cases occur in the nasal area and upper aerodigestive tract. However, occurrence in non-nasal sites such as the skin, gastrointestinal tract and testis is also observed."
Kwong - Hematol Oncol 1997 abstract / PubMedNonnasal lymphoma expressing the natural killer cell marker CD56: A clinicopathologic study of 49 cases of an uncommon agressive neoplasm. KC John, VC Sin, KF Wong, CS Ng, WYW Tsang, CH Chan, MMC Cheung, WH Lau. Blood 1997 Jun 15;89(12):4501-4513. "The nasal-type NK/T-cell lymphoma show distinctive clinicopathologic features and a very strong association with EBV."
John / Blood 1997 full articleAngiocentric T-cell lymphoma presenting as lethal midline granuloma. PY Lee, NJ Freeman, J Khorsand, MA Weinstock. Int J Dermatol 1997 Jun;36(6):419-427.
Lee - Int J Dermatol 1997 abstract / PubMed[Detection of Epstein-Barr virus DNA in malignant lymphomas]. N Kuljic-Kapulica. Vojnosanit Pregl 1997 Sep;54(5):465-468.
Kuljik-Kapulica - Vojnosanit Pregl 1997 abstract / PubMedIntegrated and episomal forms of Epstein-Barr virus (EBV) in EBV associated disease. K Oshima, J Suzumiya, M Kanda, M Kikuchi. Cancer Lett 1998 Jan 9;122(1-2):43-50.
Ohshima - Cancer Lett 1998 abstract / PubMed[Epstein-Barr virus infection and expression of T-cell intracellular antigen-1 (TIA-1) in intestinal T-cell lymphoma.] X Ren, W Liu, G Li, F Li, S Zhang. Zhonghua Bing Li Xue Za Zhi 1999 Oct;28(5):348-351. "Intestinal T-cell lymphoma may be an EBV-associated extranodal NK/T cell lymphoma."
Ren - Zhonghua Bing Li Xue Za Zhi 1999 abstract / PubMedSinonasal lymphoma: a clinicopathologic analysis of 58 cases from the Massachusetts General Hospital. I Cuadra-Garcia, GM Prouix, CL Wu, CC Wang, BZ Pilch, NL Harris, JA Ferry. Am J Surg Pathol 1999 Nov;23(11):1356-1369.
Cuadra-Garcia - Am J Surg Pathol 1999 abstract / PubMedEpstein-Barr virus (EBV)-infected cells were frequently but
dispersely detected in T-cell lymphomas of various types by in situ
hybridization with an RNA probe specific to EBV-specific nuclear
antigen 1. T Yamamoto, Y Nakamura, K Kishimoto, H Takeuchi, M
Shirakata, T Mitsuya, K Hirai. Virus Res 1999 Dec 1;65(1):43-55. "Using
ISH with improved antisense RNA probe specific to EBNA-1 mRNA, the
virus was detected in 19 (59%) of 32 cases, whereas the EBER1
transcript was found in only 15 (47%) of 32 cases by conventional
EBER-ISH, resulting in 21 EBV-positive cases (66%) by combining the two
methods."
Skin is the frequent site for involvement of peripheral T-cell and natural killer cell lymphomas in Korea. KH Cho, WW Choi, CS Youn, CW Kim, DS Heo. J Dermatol 2000 Aug;27(8):500-507.
Cho - J Dermatol 2000 abstract / PubMedEpstein-Barr virus-infected natural killer cell leukemia. K Akashi, S Mizuno. Leuk Lymphoma 2000 Dec;40(1-2):57-66. Review; discussion of hemophagocytic lymphohistiocytosis.
Akashi - Leuk Lymphoma 2000 abstract / PubMed(No title). M Koch, GJ Blatterspiel, G Niedobitek, J Constantinidis. Laryngorhinootologie 2001 Jul;80(7):410-415. Case & review.
Koch - Laryngorhinootologie 2001 abstract / PubMedDiagnostic and prognostic implications of circulating cell-free Epstein-Barr virus DNA in natural killer/T cell lymphoma. KI Lei, LY Chan, WY Chan, PJ Johnson, YM Lo. Clin Cancer Res 2002 Jan;8(1):29-34. "Plasma EBV DNA, as measured by real-time quantitative PCR, is a useful tumor marker for diagnosis, disease monitoring, and prediction of outcome in patients with NK/T cell lymphoma."
Lei - Clin Cancer Res 2002 abstract / PubMedEpstein-barr virus-associated non-Hodgkin's lymphoma of B-cell
origin, Hodgkin's disease, acute leukemia, and systemic lupus
erythematosus: a serologic and molecular analysis. W Mitarnun, J
Pradutkanchana, S Takao, V Saechan, S Suwiwat, T Ishida. J Med Assoc
Thai 2002 May;85(5):552-9. In 58 patients, "EBV internal repeat-1
region (IR-1) in peripheral blood CD3+ cells was detected in 10 of 14
patients (71.5%) with NHL-B, 3 of 8 patients (37.5%) with Hodgkin's
disease, 1 of 6 patients (16.7%) with acute leukemia, 4 of 9 patients
(44.5%) with SLE, and was not detected in any of the 21 patients with
other diseases."
Primary nasopharyngeal non-Hodgkin lymphoma and its relationship with Epstein-Barr virus infection. B Zhang, Y Zong, J He, B Zhong, S Lin. Chin Med J (Engl) 2003 Jun;116(6):913-917. "The percentages of EBV infection differed among the 3 major immunophenotypes (B cell: 11.36%, 5/44; peripheral T cell: 81.82%, 18/22; NK/T cell: 100%, 7/7)."
Zhang / Chin Med J (Engl) 2003 full articleNasal NK/T cell lymphoma in Taiwan: a clinicopathologic study of 22
cases, with analysis of histologic subtypes, Epstein-Barr virus LMP-1
gene association, and treatment modalities. TT Kuo, LY Shih, NM Tsang.
Int J Surg Pathol 2004 Oct;12(4):375-387. "All 22 cases were positive
for EBV by polymerase chain reaction and Epstein-Barr virus early RNA
(EBER) in-situ hybridization."
Epstein-Barr viral infection in extranodal lymphoma of the head and
neck: correlation with prognosis and response to treatment. AA
Bahnassy, AR Zekri, N Asaad, S El-Houssini, HM Khalid, LM Sedky, NM
Mokhtar. Histopathology 2006 Apr;48(5):516-528. "The study included 50
PELHN (11 cases in the nose and paranasal sinuses, 11 in the
nasopharynx, 13 in the tonsils, seven in the oropharynx and eight in
the oral cavity), five reactive lymph nodes, 15 normal nasopharyngeal
tissue and 25 throat washes of healthy subjects from Egypt.... EBV was
detected in 90% and 70% of the cases using EBER in situ hybridization
and PCR, respectively. All cases of nasal type lymphoma were positive
for EBV."
Tissue markers of Epstein-Bar virus (EBV) infection in B-cell
non-Hodgkin's lymphomas. A Kasprzak, R Spachacz, A Hałoń, M Jeleń, K
Stefańska, J Wachowiak, E Trejster, M Zabel. Med Wieku Rozwoj 2006
Jul-Sep;10(3 Pt 1):639-648. Archive tissue material from 26 children
and from 27 adults with B-cell NHLs, using immunocytochemical
techniques, in situ hybridisation, and PCR. "The detectability and
expression of EBV infection were significantly higher in children with
B-cell NHLs as compared to adult patients. Expression of EBNA2 and LMP1
and that of EBERs in B-cell NHLs involved mainly cells of CD20(+)
phenotype. Positive correlation was confirmed between expression of
EBNA2 and LMP1 as well as between expression of the two proteins and
EBERs in children with B-cell NHLs. Also in children with B-cell NHLs,
type III latency form dominated. In adults the latency forms were more
variable. We have demonstrated a novel form of EVB latency with no
EBERs expression, noted in children as well as in adults with B-cell
NHLs."
[Nasal and pharyngeal non-Hodgkin lymphomas and their relationship
with Epstein-Barr virus: a report of 158 cases]. YJ He, XS Jia, K
Hasui, EH Wang, AG He. Zhonghua Bing Li Xue Za Zhi 2007
Feb;36(2):94-97. "Among 99 cases studied by EBER-1 in situ
hybridization, a positive detection was seen in 70/71 cases (98.6%) of
extranodal NK/T cell lymphoma (nasal type), 8/12 cases (66.7%) of T
cell lymphoma, and 7/16 cases (43.8%) of B cell lymphoma."
Nasal natural killer/T-cell lymphoma and its association with type
"i"/XhoI loss strain Epstein-Barr virus in Chile. ME Cabrera, Y Eizuru,
T Itoh, C Koriyama, Y Tashiro, S Ding, S Rey, S Akiba, A Corvalan. J
Clin Pathol 2007 Jun;60(6):656-660. 7 out of 9 (78%) of WHO-criteria
nasal NK/T-cell lymphomas were positive for EBV.
EBV viral load in tumor tissue is an important prognostic indicator
for nasal NK/T-cell lymphoma. PP Hsieh, CL Tung, AB Chan, JB Liao, JS
Wang, HH Tseng, HH Su, KC Chang, CC Chang. Am J Clin Pathol 2007
Oct;128(4):579-584. 19 cases. "Patients with a low EBV viral load
(<1 copy per cell) more frequently survived for more than 2 years
compared with patients with a high EBV viral load (>/=1 copies/cell)
(7/7 vs 3/9; P = .014; Fisher exact test). Furthermore, the patients
with low EBV viral loads had a better overall survival than patients
with high viral loads (50% accumulative survival: not reached vs 4-5
months; Kaplan-Meier survival analysis; P = .049). In contrast, the
overall survival of the patients did not correlate with the extent of
lesion, age, stage, necrosis, histologic subtypes, CD56 expression, or
angiocentric or angiodestructive growth pattern."
Epstein-Barr virus infection and risk of lymphoma: immunoblot
analysis of antibody responses against EBV-related proteins in a large
series of lymphoma subjects and matched controls. S de Sanjosé,
R Bosch, T Schouten, S Verkuijlen, A Nieters, L Foretova, M
Maynadié, PL Cocco, A Staines, N Becker, P Brennan, Y Benavente,
P Boffetta, CJ Meijer, JM Middeldorp. Int J Cancer 2007 Oct
15;121(8):1806-1812. 1,085 incident lymphoma cases from Spain, France,
Germany, Czech Republic, Italy and 1,153 age, sex and country matched
controls. An abnormal reactive pattern to EBV was observed in 20.9% of
2,238 included subjects with an increased proportion of cases
presenting ab_EBV as compared to the control population (23.9% vs.
18.0% p = 0.001). Ab_EBV positivity was a risk factor for all lymphomas
combined (odds ratio [OR] = 1.42, 95% confidence interval
[CI]=1.15-1.74), and specifically for chronic lymphocytic leukaemia (OR
= 2.96, 95%CI = 2.22-3.95).
Correlation of immunophenotype of sinonasal non-Hodgkin's lymphoma
to Epstein-Barr virus infection. YF Feng, QL Wu, YS Zong. Ai Zheng 2007
Nov;26(11):1170-1176. "Seventy-one sinonasal NHLs were found in all 1
412 NHLs (71/1 412, 5.03%). Only 57 out of the 71 NHL biopsy tissues
were suitable for this study. The median age of the patients was 50
years (ranged from 3 to 75 years). There were 38 males and 19 females.
Forty-four sinonasal NHLs (44/57, 77.19%) were NK/T-cell lymphoma,
nasal type, all of which were infected with EBV."
Quantitative analysis of cell-free Epstein-Barr virus DNA in the
plasma of patients with peripheral T-cell and NK-cell lymphomas and
peripheral T-cell proliferative diseases. S Suwiwat, J Pradutkanchana,
T Ishida, W Mitarnun. J Clin Virol 2007 Dec;40(4):277-283. Cell-free
EBV DNA was detected in 32/38 (84%) of peripheral T-cell and NK-cell
lymphoma patients and 5/7 (71%) of peripheral T-cell proliferative
disease patients, but not in the 45 controls.
Arginine butyrate-induced susceptibility to ganciclovir in an Epstein-Barr induced lymphoma. SJ Mentzer, J Fingeroth, JJ Reilly, SP Perrine, DV Faller, Blood Cells Mol Dis 1998 Jun;24(2):114-123. "[A]ntiviral therapy with synthetic nucleosides such as ganciclovir are ineffective because the genes that render the virus susceptible to therapy are not expressed in EBV+ lymphomas... Arginine butyrate was not only effective in inducing EBV thymidine kinase transcription, but also acted synergistically with the antiviral agent ganciclovir to inhibit cell proliferation and decrease cell viability."
Mentzer - Blood Cells Mol Dis 1998 abstract / PubMedHerpesvirus-specific CD8 T cell immunity in old age: cytomegalovirus
impairs the response to a coresident EBV infection. N Khan, A Hislop, N
Gudgeon, M Cobbold, R Khanna, L Nayak, AB Rickinson, PA Moss. J Immunol
2004;173(12):7481-7489. "Interestingly, the effect of age upon
EBV-specific responses depends upon donor CMV sero-status. In CMV
seropositive donors, the magnitude of the EBV-specific immune response
is stable with age, but in CMV seronegative donors, the response to EBV
increases significantly with age. By contrast, the influenza-specific
CD8 T cell immune response decreases with age, independent of CMV
status. The functional activity of the herpesvirus-specific immune
response decreases in elderly donors, although the characteristic
phenotypes of CMV- and EBV-specific memory populations are retained.
This demonstrates that aging is associated with a marked accumulation
of CMV-specific CD8 T cells together with a decrease in immediate
effector function. Moreover, infection with CMV can reduce
prevailing levels of immunity to EBV, another persistent
virus. These results
suggest that carriage of CMV may be detrimental to the immunocompetent
host by suppressing heterologous virus-specific immunity during aging."
Interferon Regulatory Factor 7 Is Associated with Epstein-Barr Virus-Transformed Central Nervous System Lymphoma and Has Oncogenic Properties. L Zhang, J Zhang, Q Lambert, CJ Der, L Del Valle, J Miklossy, K Khalili, Y Zhou, JS Pagano. J Virol 2004 Dec;78(23):12987-12995.
Zhang / J Virology 2004 Full ArticleLMP1 strain variants: biological and molecular properties. BA
Mainou, N Raab-Traub. J Virol 2006 Jul;80(13):6458-6468. "LMP1 can
activate a wide array of signaling pathways, including
phosphatidylinositol 3-kinase (PI3K)-Akt and NF-kappaB. Six sequence
variants of LMP1, termed Alaskan, China 1, China 2, Med+, Med-, and NC,
have been identified, and individuals can be infected with multiple
variants. The frequencies of detection of these variants differ for
various EBV-associated malignancies from different geographic
regions.... While all the variants activated the PI3K-Akt signaling
pathway to similar extents, the Alaskan, China 1, and Med+ variants had
limited binding to the E3 ubiquitin ligase component homologue of Slimb
and had slightly enhanced NF-kappaB signaling."
A molecular link between malaria and Epstein-Barr virus
reactivation. A Chêne, D Donati, AO Guerreiro-Cacais, V Levitsky,
Q Chen, KI Falk, J Orem, F Kironde, M Wahlgren, MT Bejarano. PLoS
Pathog 2007 Jun;3(6):e80. "We show that CIDR1alpha binds to the
EBV-positive B cell line Akata and increases the number of cells
switching to the viral lytic cycle as measured by green fluorescent
protein (GFP) expression driven by a lytic promoter. The virus
production in CIDR1alpha-exposed cultures was directly proportional to
the number of GFP-positive Akata cells (lytic EBV) and to the increased
expression of the EBV lytic promoter BZLF1. Furthermore, CIDR1alpha
stimulated the production of EBV in peripheral blood mononuclear cells
derived from healthy donors and children with BL. Our results suggest
that P. falciparum antigens such as CIDR1alpha can directly induce EBV
reactivation during malaria infection that may increase the risk of BL
development for children living in malaria-endemic areas. To our
knowledge, this is the first report to show that a microbial protein
can drive a latently infected B cell into EBV replication."
Epstein-Barr Virus Infection of Langerhans Cell Precursors as a
Mechanism of Oral Epithelial Entry, Persistence, and Reactivation. DM
Walling, AJ Ray, JE Nichols, CM Flaitz, CM Nichols. J Virol 2007
Jul;81(13):7249-7268. "In this study, we present the first evidence
demonstrating that EBV latently infects a unique subset of blood-borne
mononuclear cells that are direct precursors to Langerhans cells and
that EBV both latently and productively infects oral
epithelium-resident cells that are likely Langerhans cells. These data
form the basis of a proposed new model of EBV transition from blood to
oral epithelium in which EBV-infected Langerhans cell precursors serve
to transport EBV to the oral epithelium as they migrate and
differentiate into oral Langerhans cells. This new model contributes
fresh insight into the natural history of EBV infection and the
pathogenesis of EBV-associated epithelial disease."
cast 08-10-08