Biomolecular analysis of a defective nontransforming Epstein-Barr virus (EBV) from a patient with chronic active EBV infection

Alfieri, Caroline; Joncas, J H

doi:10.1128/jvi.61.10.3306-3309.1987

Cited by 35 publications

(12 citation statements)

References 14 publications

(5 reference statements)

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“…In this context, direct cloning has shown that defective genomes, particularly with deletions and/or rearrangements in the EBNA2 gene region, can be generated in the oropharynx as aberrant products of virus replication (44,48,50). Oropharyngeal persistence of a defective viral strain has been observed in replicative lesions (4,47,49) and in one case has also been detected in the blood (47). However, in most cases it seems to us unlikely that viruses without transforming function would efficiently colonize the B-cell pool (46).…”

Section: Discussionmentioning

confidence: 99%

Frequency of multiple Epstein-Barr virus infections in T-cell-immunocompromised individuals

Yao

Tierney

Croom-Carter

et al. 1996

J Virol

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The Epstein-Barr virus (EBV) carrier state is characterized by latent infection of the general B-cell pool and by chronic virus replication at oropharyngeal sites. In Caucasian populations, most healthy carriers seem to harbor one dominant transforming virus strain, usually of type 1 rather than type 2, which persists over time and is detectable both in the blood and in the throat. This finding implies that once the virus carrier state is established, both viral reservoirs are largely if not completely protected from infection with additional strains. However, it is not known which facets of the immune response offer that protection. Here we address this question by a detailed study of EBV carriage in patients T-cell immunocompromised as a result of chronic human immunodeficiency virus (HIV) infection. Resident EBV strains were rescued from blood and from throat washings by using an in vitro transformation assay which aims to minimize bias toward faster-growing transformants; in this way, a mean of 16 independent isolations were made from each of 35 HIV-positive (predominantly male homosexual) patients. These virus isolates were characterized first at the DNA level by PCR amplification across type-specific polymorphisms in the EBNA2 and EBNA3C genes and across the 30-bp deletion and 33-bp repeat loci in the LMP1 gene and then at the protein level by immunoblotting for the strain-specific "EBNAprint" of EBNA1, -2, and -3C molecular weights. By these criteria, 18 of 35 patients harbored only one detectable EBV strain, usually of type 1, as do healthy carriers. However, the other 17 patients showed clear evidence of multiple infection with different EBV strains. In eight cases these strains were of the same type, again usually type 1, and were more often found coresident in throat washings than in the blood. By contrast, a further nine patients gave evidence of coinfection with type 1 and type 2 strains, and in these cases both virus types were detectable in the blood as well as in the throat. Immunological assays on these HIV-positive patients as a group showed a marked impairment of T-cell responses, reflected in reduced levels of EBV-specific cytotoxic T-cell memory, but an elevation of humoral responses, reflected in raised antibody titers to the EBV envelope glycoprotein gp340 and by the maintenance of virus neutralizing antibodies in serum. We infer that selective impairment of the T-cell system predisposes the host to infection with additional exogenously transmitted EBV strains.

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Section: Discussionmentioning

confidence: 99%

Frequency of multiple Epstein-Barr virus infections in T-cell-immunocompromised individuals

Yao

Tierney

Croom-Carter

et al. 1996

J Virol

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“…Since neither EBV type 2 nor other additional EBV type 1 strains were found in lymphatic tissues from either child, it is suggested that in addition to genetic and immunological factors, this EBNA2-variant EBV substrain substantially contributed to the severe course of the disease. Other investigators have found transforming-incompetent defective EBV strains in B cells of some patients with chronic active EBV infection [Alfieri et al, 1987;Schooley et al, 19861. It is not known if these EBV isolates carried an EBNAB mutation as described here.…”

Section: Discussionmentioning

confidence: 97%

Detection of a nuclear antigen 2 (EBNA2)-variant Epstein-Barr virus strain in two siblings with fatal lymphoproliferative disease

1996

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An EBV type 1 variant strain was detected in two Turkish siblings (boy and girl), who both suffered and died from similar progressive Epstein-Barr virus (EBV)-associated lymphoproliferative disease. Molecular characterisation of this EBV isolate revealed a 51bp-deletion and six nucleotide changes within the Epstein-Barr nuclear antigen 2 (EBNA2). Both isolates contained EBV type 2 sequences in the Epstein-Barr virus-encoded small RNAs (EBER), which are 40 kb proximal to EBNA2. Sequencing of the EBV isolates in a region of Epstein-Barr nuclear antigen 3 (EBNA3a), which is 40 kb distal to EBNA2, revealed the normal EBV type 1 sequence of laboratory strain B95-8. This EBV isolate may represent a distinct wild type EBV strain with altered biological properties. It is suggested that this EBNA2-variant strain may be responsible at least in part for the severe clinical course in both affected children.

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“…The observation of a naturally occurring HR-I-like EBV is rare. To our knowledge, the only previous reports describing such a virus isolate were published by Alfieri et al (1984) and Alfieri and Joncas (1987) who obtained an HR-1-like virus from a patient with chronic active EBV infection. Our data confirm those previous reports that naturally occurring lytic non-transforming isolates of EBV may exist.…”

Section: Discussionmentioning

confidence: 99%

Expression of the epstein‐barr virus genome in a nasopharyngeal carcinoma epithelial tumor cell line

Zhang

Yao

Zhu

et al. 1990

Intl Journal of Cancer

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An epithelial tumor cell line was recently established from a biopsy specimen of a nasopharyngeal carcinoma (NPC), and designated HONE-I. Uncloned (parental) HONE-I and HONE-I clone (C)-40 cells were found to contain latent Epstein-Barr virus (EBV). Expression of the latent EBV genome in HONE-I C-40 cells has been examined. It was possible to detect a small percentage of cells spontaneously synthesizing EBV early antigen (EA) and virus capsid antigen (VCA) by immunofluorescence (IF). In addition, the EBV nuclear antigens (EBNA-I and EBNA-2), as well as the EBV latent membrane protein (LMP) were detected in the HONE-I cells. Attempts were made to induce the latent EBV genome in these cells with iododeoxyuridine (IUdR). We observed a significant increase in the number of EA/VCA-positive cells, an increase in EBV DNA, the synthesis of virus particles, and the rescue of infectious virus after treatment of HONE-I C-40 cells with IUdR. The HONE-I C-40 cells should facilitate studies of the expression and regulation of the EBV genome in NPC epithelial tumor cells, which have not previously been available.

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Biomolecular analysis of a defective nontransforming Epstein-Barr virus (EBV) from a patient with chronic active EBV infection

Cited by 35 publications

References 14 publications

Frequency of multiple Epstein-Barr virus infections in T-cell-immunocompromised individuals

Frequency of multiple Epstein-Barr virus infections in T-cell-immunocompromised individuals

Detection of a nuclear antigen 2 (EBNA2)-variant Epstein-Barr virus strain in two siblings with fatal lymphoproliferative disease

Expression of the epstein‐barr virus genome in a nasopharyngeal carcinoma epithelial tumor cell line

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