Evolution of Two Types of Rhesus Lymphocryptovirus Similar to Type 1 and Type 2 Epstein-Barr Virus

ABSTRACT Rhesus monkeys and other nonhuman Old World primates are naturally infected with lymphocryptoviruses (LCV) that are closely related to Epstein-Barr virus (EBV). A rhesus LCV isolate (208-95) was derived from a B-cell lymphoma in a simian immunodeficiency virus-infected rhesus macaque. The EBNA-2 homologues from 208-95 and a previous rhesus LCV isolate (LCL8664) were polymorphic on immunoblotting, so the EBNA-2 genes from these two rhesus LCV were cloned, sequenced, and compared. The EBNA-2 genes have 40% nucleotide and 41% amino acid identities, and the differences are similar to those between the type 1 and type 2 EBV EBNA-2. Sequence from a portion of the LMP1 gene which is extremely divergent among different LCV was virtually identical between the 208-95 and LCL8664 strains, confirming a common rhesus LCV background. Thus, the EBNA-2 polymorphism defines the presence of two different rhesus LCV types, and both rhesus LCV types were found to be prevalent in the rhesus monkey population at the New England Regional Primate Research Center. The existence of two rhesus LCV types suggests that the selective pressure for the evolution of two LCV types is shared by human and nonhuman primate hosts.

Download Full-text

The Epstein-Barr Virus DNA Polymerase Transactivates the Human Immunodeficiency Virus Type 1 5′ Long Terminal Repeat

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1993.2036 ◽

1993 ◽

Vol 195 (1) ◽

pp. 242-249 ◽

Cited By ~ 9

Author(s):

J.C. Lin

Keyword(s):

Human Immunodeficiency Virus ◽

Long Terminal Repeat ◽

Dna Polymerase ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Epstein Barr Virus ◽

Barr Virus ◽

Immunodeficiency Virus ◽

Epstein Barr

Download Full-text

Epstein Barr virus genomes reveal population structure and type 1 association with endemic Burkitt lymphoma

10.1101/689216 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yasin Kaymaz ◽

Cliff I. Oduor ◽

Ozkan Aydemir ◽

Micah A. Luftig ◽

Juliana A. Otieno ◽

...

Keyword(s):

Population Structure ◽

Burkitt Lymphoma ◽

Epstein Barr Virus ◽

Genome Wide Association ◽

Viral Dna ◽

Barr Virus ◽

Genome Wide ◽

Epstein Barr

AbstractEndemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is associated with malaria and Epstein Barr virus (EBV). In order to better understand the role of EBV in eBL, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (N=58) and healthy controls (N=40) residing in the same geographic region in Kenya. Comparing cases and controls, we found that EBV type 1 was significantly associated with eBL with 74.5% of patients (41/55) versus 47.5% of healthy children (19/40) carrying type 1 (OR=3.24, 95% CI=1.36 - 7.71,P=0.007). Controlling for EBV type, we also performed a genome-wide association study identifying 6 nonsynonymous variants in the genes EBNA1, EBNA2, BcLF1, and BARF1 that were enriched in eBL patients. Additionally, we observed that viruses isolated from plasma of eBL patients were identical to their tumor counterpart consistent with circulating viral DNA originating from the tumor. We also detected three intertypic recombinants carrying type 1 EBNA2 and type 2 EBNA3 regions as well as one novel genome with a 20 kb deletion resulting in the loss of multiple lytic and virion genes. Comparing EBV types, genes show differential variation rates as type 1 appears to be more divergent. Besides, type 2 demonstrates novel substructures. Overall, our findings address the complexities of EBV population structure and provide new insight into viral variation, which has the potential to influence eBL oncogenesis.Key PointsEBV type 1 is more prevalent in eBL patients compared to the geographically matched healthy control group.Genome-wide association analysis between cases and controls identifies 6 eBL-associated nonsynonymous variants in EBNA1, EBNA2, BcLF1, and BARF1 genes.Analysis of population structure reveals that EBV type 2 exists as two genomic sub groups.

Download Full-text

Second-site homologous recombination in Epstein-Barr virus: insertion of type 1 EBNA 3 genes in place of type 2 has no effect on in vitro infection.

Journal of Virology ◽

10.1128/jvi.66.2.780-789.1992 ◽

1992 ◽

Vol 66 (2) ◽

pp. 780-789 ◽

Cited By ~ 28

Author(s):

B Tomkinson ◽

E Kieff

Keyword(s):

Homologous Recombination ◽

Epstein Barr Virus ◽

Barr Virus ◽

Epstein Barr

Download Full-text

Common Epstein-Barr virus (EBV) type-1 variant strains in both malignant and benign EBV-associated disorders

Blood ◽

10.1182/blood.v87.4.1579.bloodjournal8741579 ◽

1996 ◽

Vol 87 (4) ◽

pp. 1579-1585 ◽

Cited By ~ 24

Author(s):

V Schuster ◽

G Ott ◽

S Seidenspinner ◽

HW Kreth

Keyword(s):

Gastric Carcinoma ◽

Epstein Barr Virus ◽

Hodgkin's Lymphoma ◽

Sequence Pattern ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr

In the present study, Epstein-Barr virus (EBV) isolates from 18 malignant tumors (angioimmunoblastic lymphadenopathy [AILD], n = 4; Hodgkin's disease [HD], n = 3; pleomorphic T-cell non-Hodgkin's lymphoma [T-NHL], n = 1; B-cell non-Hodgkin's lymphoma [B-NHL], n = 8; gastric carcinoma, n = 2) as well as from 10 tonsils of EBV- seropositive children and from peripheral blood mononuclear cells of 12 children with uncomplicated infectious mononucleosis (IM) and of a boy with severe chronic active EBV infection were genotyped in the EBV nuclear antigen-2 (EBNA-2) gene. A total of 40 of 41 isolates harbored EBV type 1; in 1 specimen (tonsil), only EBV type 2 was found. Further molecular characterization of EBV type-1 wild-type isolates in the EBNA- 2 gene and in the 40-kb distant EBV-encoded small RNAs (EBER) region showed that different groups of stable EBV type-1 variant strains exist in vivo both in benign and malignant lymphatic tissue. Group 1 is composed of EBV type-1 isolates (B-NHL, n = 3; T-NHL, n = 1; HD, n = 1; IM, n = 4) that showed a B95–8-like DNA sequence pattern in both viral genes. Group 2 isolates (HD, n = 1; AILD, n = B-NHL, n = 1; tonsils of EBV-seropositive children, n = 9; IM, n = 20 showed a nucleotide change at position 49095 in the EBNA-2 gene, leading to an amino acid substitution (Pro-->Ser), and EBV type-2 sequences in the EBER region. EBV type-1 isolates that fall into group 3 (AILD, n = 3; HD, n = 1; B- NHL, n = 4; gastric carcinoma, n = 2; IM, n = 6; severe chronic active EBV infection, n = 1) were characterized by typical nucleotide changes and a 3-bp insertion (CTC; extra Leu residue) in the EBNA-2 gene and an EBV type-2-specific sequence pattern in the EBER region. These EBV type- 1 variant strains may represent the most prevalent circulating EBV type- 1 strains in the exposed population and seem not to be restricted to a certain EBV-associated disease or tumor type. However, analysis of more EBV isolates from benign and malignant lesions must show whether more EBV type-1 substrains exist in vivo.

Download Full-text

Human immunodeficiency virus type 1 Tat protein modulates cell cycle and apoptosis in Epstein–Barr virus-immortalized B cells

Experimental Cell Research ◽

10.1016/j.yexcr.2004.01.018 ◽

2004 ◽

Vol 295 (2) ◽

pp. 539-548 ◽

Cited By ~ 15

Author(s):

Eva Colombrino ◽

Elisabetta Rossi ◽

Gianna Ballon ◽

Liliana Terrin ◽

Stefano Indraccolo ◽

...

Keyword(s):

Cell Cycle ◽

Human Immunodeficiency Virus ◽

B Cells ◽

Human Immunodeficiency Virus Type ◽

Epstein Barr Virus ◽

Tat Protein ◽

Barr Virus ◽

Immunodeficiency Virus ◽

Epstein Barr

Download Full-text

The consistent association between Epstein-Barr virus and Hodgkin's disease in children in Kenya

Blood ◽

10.1182/blood.v87.9.3828.bloodjournal8793828 ◽

1996 ◽

Vol 87 (9) ◽

pp. 3828-3836 ◽

Cited By ~ 60

Author(s):

M Weinreb ◽

PJ Day ◽

F Niggli ◽

EK Green ◽

AO Nyong'o ◽

...

Keyword(s):

Epstein Barr Virus ◽

Hodgkin’S Disease ◽

Mixed Cellularity ◽

Lymphocyte Depletion ◽

Barr Virus ◽

Nodular Sclerosis ◽

Epstein Barr ◽

Dual Infections

Recent studies have suggested that Epstein-Barr virus (EBV) may play a role in the etiology of Hodgkin's disease (HD). In a previous study, we used a latent membrane protein 1 (LMP1)-specific antibodies to examine archival material from 74 British children with HD and found 50% of cases to be positive. It is known that there are geographic and ethnic variations in the incidence of HD. We have investigated LMP1 status in formalin-fixed, paraffin wax-embedded lymph nodes with HD involvement from 53 children and 48 adults from Kenya using immunohistochemical staining. We also developed sensitive and specific in vitro gene amplification protocols for examining the EBV strain type in such material using several combinations of primers derived from the EBNA 2 and EBNA 3 coding regions. LMP1 positivity was present in 100% of the pediatric cases (two lymphocyte-predominant, 25 nodular sclerosis, 16 mixed cellularity, 5 lymphocyte depletion, and 5 unclassified) and in 66% of the adult cases (two of three lymphocyte-predominant, 26 of 39 nodular, sclerosis, two of two mixed cellularity, and two of four lymphocyte depletion). Tests to type the EBV strain were undertaken in 25 EBV-positive pediatric cases. A combination of type-specific polymerase chain reactions for EBNA 2 and EBNA 3C genes indicated that seven patients had type 1, eight had type 2, and 10 had dual infections with both types. Five cases with dual infections were further investigated using a sensitive in situ hybridization for the EBV- encoded, small nuclear nonpolyadenylated RNAs (EBERs). EBER transcripts were detected in Reed-Sternberg and Hodgkin cells and in occasional infiltrating lymphocytes. These observations indicate that in Kenya EBV is consistently associated with pediatric cases of HD, and that biopsies from a number of such cases appear to carry both type 1 and type 2 viral sequences.

Download Full-text