Reservoir For Epstein-Barr Virus Research Articles

Prevention of post-transplant lymphoproliferative disorder in pediatric kidney transplant recipients.

Post-transplant lymphoproliferative disorder (PTLD) is a devastating complication of immunosuppressive treatment in both solid organ transplantations (SOT) and hematopoietic stem cell transplantations (HSCT). Epstein-Barr virus (EBV) infection precedes PTLD in 90% of patients. Rituximab, a monoclonal anti-CD20 antibody, depletes B-lymphocytes, which are the ultimate reservoir for EBV. Although rituximab therapy is commonly used as a preventive measure for PTLD in high-risk HSCT, it is not established in SOT. Pediatric kidney transplant recipients (PKTR) underwent routine EBV-PCR surveillance. Patients with increasing viral loads, despite immunosuppressive dose reduction, were managed with preventive rituximab therapy. Between 2012 and 2023, we identified eight episodes of asymptomatic EBV-PCR-positive blood tests in seven out of 65 PKTR (11%) under our care. EBV DNAemia emerged 120-720days post-transplantation. Five of seven patients with EBV DNAemia (71%) were EBV-seronegative prior to transplantation. All five patients did not respond to MMF dose reduction and were therefore treated with preventive rituximab therapy. Following this treatment, EBV PCR clearance was observed in all patients with only minimal complications. PKTR who are EBV-naïve prior to transplantation are expected to have a higher prevalence of EBV DNAemia. We found that PKTR who were EBV seronegative prior to transplantation were less likely to achieve EBV clearance in response to immunosuppression dose reduction. We suggest that rituximab therapy in PKTR may be safe and effective in EBV clearance and PTLD prevention.

Razvoj produženog COVID-a kao posledice kompleksnog odnosa između Epštajn-Bar virusa i našeg imunskog sistema

Introduction: The pathophysiological development of long COVID (LC) is still insufficiently known. However, post infection fatigue syndromes were seen before, among other pathogens including Epstein-Barr virus (EBV). Considering EBV reservoir in COVID-19 patients, this review aims to present current knowledge related to EBV role in development of LC and with the potential diagnostic utility. EBV infection: Following the primary lytic infection of epithelial oropharyngeal and nasopharyngeal cells EBV establishes a very complex mechanism of lifelong survival in B cells. Latent infection with occasional viral reactivations constantly challenges the host's immune response. In individuals with immune imbalance including COVID-19, it could drive long-term consequences. EBV and COVID-19: The activity of EBV has been shown as the most prevalent human herpesvirus infection in COVID-19 population (41%). Correlation between lymphocytopenia-induced disability to remove the EBV, increases in EBV DNA viremia and COVID-19 complications have also been reported. EBV and long COVID: The positivity of EBV DNA during acute SARS-CoV-2 infection predicted the presence of symptoms up to 60 days after COVID-19. Association between EBV infection and symptoms such as brain fog, fatigue, arthralgia and skin rashes have been also described in post infection sequelae ME/CFS. Anti-EBV early antigen-diffuse (EA-D) IgG antibodies were detectable among two-thirds of respondents experiencing LC. Increases in anti-EBNA1 IgG levels analyzed months following COVID-19 onset in convalescent LC population could serve as a potential marker of EBV reactivation at the time of acute SARS-CoV-2 infection. Some authors also managed to show anti-EBV viral capsid antigen (VCA) IgM seropositivity in half of COVID-19 patients indicating of either coinfection or EBV reactivation. Conclusion: As a multisystemic illness, LC is without a defined spectrum of diagnostic and treatment options. Whereas EBV reactivation alone or together with other risk factors drives LC symptoms, further prospective studies involving different cohorts and tissue reservoirs are necessary to understand underlying biological mechanisms.

Detection of Epstein-Barr virus in systemic sclerosis patients: A molecular and serological based study.

This study aimed to evaluate an association between Epstein-Barr virus (EBV) and systemic sclerosis (SSc). One hundred and fifty (138 female, 12 male) consecutive adult SSc patients fulfilling the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria were included in this cross-sectional study. Serological analysis by line blot for class immunoglobulin G (IgG) and IgM antibodies against EBV antigen (EBV capsid antigen [VCA] gp125, VCA p19, EBNA-1, p22, EA-D) and quantification of EBV DNA in whole blood by real-time polymerase chain reaction was performed. Class IgM antibodies against VCA gp125 (22.8% vs 0%, P < .0002), VCA p19 (55.7% vs 4.4%, P < .0001), EBNA1 (35.7% vs 0%, P < .0001), p22 (24.2% vs 0%, P < .0001), EA-D (14.2% vs 2.2%, P < .04), and class IgG antibodies against p22 (95.7% vs 82.2%, P < .02) and EA-D (54.2% vs 0%, P < .0001) reactivities were significantly higher in SSc patients than in controls. The past infection was significantly associated with the control group (42.8% vs 91%, P < .0001); and the viral reactivation was significantly associated with the SSc group (55.7% vs 4.4%, P < .0001). Only three (2%) out of 150 SSc patients were positive for EBV DNA, similar to the control group (2%) (P > .9). The study shows a strong serological association of EBV (reactivation stage) with SSc patients in the absence of viral DNA in the circulation, indicating the EBV reservoir or tropism presence elsewhere.

Epstein-Barr virus (EBV) in periodontal sites of human immunodeficiency virus (HIV)-positive individuals in North Brazil: a cross-sectional study.

This study aimed to investigate the Epstein-Barr virus (EBV) prevalence and viral load in subgingival sites of human immunodeficiency virus type 1 (HIV-1) positive (HIV+) individuals, correlating subgingival EBV load to the clinical periodontal condition, HIV systemic load, EBV systemic load, and use of antiretroviral therapy (ART). Ninety individuals were recruited and divided into three categories: those without periodontal disease (G1), with gingivitis (G2), and with periodontitis (G3). Subgingival biofilm and blood samples were analyzed by quantitative polymerase chain reactions (qPCR). A questionnaire was administered to collect general information about patients, and data regarding HIV and use of ART were accessed from their medical records. EBV was detected in 85.6% of the samples. Comparing subgingival and systemic load of EBV in G1, G2, and G3, there was a statistical difference only in G3 (3.93 log10 copies/mL and 5.47 log10 copies/mL, respectively; P = .014), where EBV load was higher in periodontal pockets than in the blood. All groups had high EBV loads in subgingival sites (> 2,000 copies/mL). A positive linear correlation between systemic HIV load and EBV subgingival load was found in G1 and G2 (r = 0.647; P < .001), but not in G3. Only G1 individuals using ART had lower subgingival EBV loads than those not using it (5.03 log10 copies/mL, and 7.14 log10 copies/mL, respectively; P = .0348). Subgingival sites, especially the periodontal pockets, are suggested to act as a reservoir of EBV in HIV+ individuals. Therefore, the identification of latent EBV infections in this easily accessible site might help to improve quality of life in patients with HIV by maintaining oral/periodontal health. In addition it might encourage new approaches in investigating EBV-associated disorders in HIV+ patients.

Epstein-Barr Virus Induces Expression of the LPAM-1 Integrin in B Cells In Vitro and In Vivo.

Epstein-Barr virus (EBV) infects the oropharynx but, surprisingly, frequently induces B cell proliferation in the gut of immunosuppressed individuals. We found that EBV infection in vitro induces the expression of the LPAM-1 integrin on tonsillar B cells and increases it on peripheral blood cells. Similarly, LPAM-1 was induced in the tonsils of patients undergoing primary infectious mononucleosis. EBV-induced LPAM-1 bound to the MAdCAM-1 addressin, which allows B cell homing to the gastrointestinal mucosa-associated lymphoid tissue (GALT). Thus, we hypothesized that EBV-induced LPAM-1 could induce relocation of infected B cells from the tonsil to the GALT. In situ hybridization with an EBER-specific probe revealed the frequent presence of EBV-infected cells in the pericolic lymph nodes of healthy individuals. Relocation of infected B cells into the GALT would expand the EBV reservoir, possibly protecting it from T cells primed in the oropharynx, and explain why EBV induces lymphoid tumors in the gut.IMPORTANCE EBV causes tumors in multiple organs, particularly in the oro- and nasopharyngeal area but also in the digestive system. This virus enters the body in the oropharynx and establishes a chronic infection in this area. The observation that the virus causes tumors in the digestive system implies that the infected cells can move to this organ. We found that EBV infection induces the expression of integrin beta 7 (ITGB7), an integrin that associates with integrin alpha 4 to form the LPAM-1 dimer. LPAM-1 is key for homing of B cells to the gastrointestinal tract, suggesting that induction of this molecule is the mechanism through which EBV-infected cells enter this organ. In favor of this hypothesis, we could also detect EBV-infected cells in the lymph nodes adjacent to the colon and in the appendix.

Expression of Epstein-Barr virus in children with sacrococcygeal pilonidal sinus determined by immunohistochemical methods

In this study, we probed whether chronic infections of skin such as pilonidal sinus could be a potential site of Epstein-Barr virus (EBV) replication. Pilonidal sinus is associated with a high recurrence rate. Therefore, we decided to determine the role of EBV's presence to explain whether it is correlated with the recurrence of pilonidal sinuses. This study was conducted on 36 patient samples with sacrococcygeal pilonidal sinus. Samples were immunohistochemically stained for EBV, CD3 and CD20 expression. Thirty-six adolescents with pilonidal disease were evaluated. EBV-positive cells were located in dermis with high inflammatory activity. EBV-positive cells stained positive for the B-cell antigen CD20 and were detected in 10 of 36 (27%) pilonidal sinus specimens. Among those who had experienced a relapse, three were positive for EBV expression. In addition, EBV expression was detected in eight cases with severe inflammation, and in two with minimal or moderate inflammation. Our study advances the field by demonstrating that similar to gastrointestinal mucosa, skin could be a reservoir for EBV. EBV was found to be restricted to B cells in skin lesions, and it was found that skin lesions with severe inflammation showed higher frequency of EBV expression in comparison to minimal or moderately inflammed skin lesions. Additionally, recurrence was more frequently observed among EBV-positive cases. These findings point out for a role of EBV infection in the recurrence of pilonidal sinuses.

Close relationship between immunoglobulin secreting‐cells and Epstein–Barr virus reservoir in patients infected with HIV

Individuals infected with HIV have higher circulating Epstein-Barr virus (EBV) DNA load compared to healthy carriers. This study investigated whether level of spontaneous immunoglobulin secreting cells, one of the major hallmarks of HIV infection, is associated with an increase of EBV DNA load in PBMCs and the spontaneous EBV lytic cycle ex vivo in patients infected with HIV. Spontaneous virus production by cells infected with EBV and EBV DNA loads in PBMCs from which CD8(+) T-cells were removed were measured in 20 HIV-aviremic and 14 HIV-viremic patients. The number of circulating immunoglobulin-secreting cells (Ig-SCs) and CD8(+) T-lymphocyte activation were also investigated. Patients with detectable HIV RNA in plasma exhibited higher spontaneous ex vivo EBV secretion and higher levels of EBV DNA in PBMCs than their aviremic counterparts. In the two groups observed, a positive correlation was found between PBMCs EBV DNA viral load and Ig-SCs, CD38(bright) expression on CD8(+) T-cells and EBV DNA load in cell culture supernatants. These findings suggest that B-cell polyclonal activation and B-cell terminal differentiation into Ig-SCs may fuel EBV DNA reservoir and promote EBV production ex vivo in patients infected with HIV.

High frequency of Epstein-Barr virus–infected lymphocytes in pilonidal cysts

Circulating memory B cells are considered as the main reservoir for Epstein-Barr virus. Several studies identified the presence of Epstein-Barr virus-infected B cells in the lesions of Crohn disease and ulcerative colitis suggesting that colon mucosa with chronic inflammation could be a potential site of Epstein-Barr virus replication. However, whether skin could be also an Epstein-Barr virus reservoir has not yet been investigated. We used pilonidal cysts as a model of skin chronic inflammation, and we found in 20 (55.6%) of 36 cases variable amounts of Epstein-Barr virus-infected cells as assessed by in situ hybridization using Epstein-Barr virus-encoded RNA probe and immunostainings. Most (95%) of the Epstein-Barr virus-positive cells were of B-cell phenotype, whereas scattered cells were double stained with Epstein-Barr virus-encoded RNA probes and T-cell markers. Epstein-Barr virus-encoded RNA+ cell density correlated with the intensity of inflammation. This density was similar to that observed in chronic diverticulitis but higher when compared with appendicitis, suggesting that chronic rather than acute inflammation facilitates the recruitment of Epstein-Barr virus-infected cells in diseased tissues. Altogether, these data suggest that, in immunocompetent patients, skin inflammatory lesions contain Epstein-Barr virus-infected cells exhibiting latency type I. Moreover, skin-like gastrointestinal mucosa is a potential site of Epstein-Barr virus replication and spreading. Our results may explain the pathogenesis of the Epstein-Barr virus-positive mucocutaneous ulcer.

Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus

Patients with the primary immunodeficiency X-linked lymphoproliferative disease (XLP), which is caused by mutations in SH2D1A, are highly susceptible to Epstein-Barr virus (EBV) infection. Nonetheless, some XLP patients demonstrate less severe clinical manifestations after primary infection. SH2D1A encodes the adaptor molecule SLAM-associated protein (SAP), which is expressed in T and natural killer cells and is required for cytotoxicity against B cells, the reservoir for EBV. It is not known why the clinical presentation of XLP is so variable. In this study, we report for the first time the occurrence of somatic reversion in XLP. Reverted SAP-expressing cells resided exclusively within the CD8(+) T cell subset, displayed a CD45RA(-)CCR7(-) effector memory phenotype, and were maintained at a stable level over time. Importantly, revertant CD8(+) SAP(+) T cells, but not SAP(-) cells, proliferated in response to EBV and killed EBV-infected B cells. As somatic reversion correlated with EBV infection, we propose that the virus exerts a selective pressure on the reverted cells, resulting in their expansion in vivo and host protection against ongoing infection.

Changes in Blood B Cell Phenotypes and Epstein‐Barr Virus Load in Chronically Human Immunodeficiency Virus–Infected Patients before and after Antiretroviral Therapy

Switched and nonswitched memory B cells, which usually constitute the main reservoirs of Epstein‐Barr virus (EBV), are rapidly depleted in patients with chronic human immunodeficiency virus (HIV) infection. Because the EBV load is frequently increased in these patients, other B cell reservoirs might participate in EBV persistence. We examined the combined expression of CD27, SIgD/G/M, CD38, CD10, CD5, CXCR5, CD62L, CD44, and CXCR3 on B cells from healthy donors (n = 30) and from HIV type 1-infected patients (n = 23) at diagnosis and after highly active antiretroviral therapy. The plasma HIV load and the DNA EBV load in peripheral blood mononuclear cells were assessed. Increased frequencies of CD38+SIgD+CD10+ B cells were found in patients with an EBV load >10(3)copies per 10(6)peripheral blood mononuclear cells and a strong depletion of memory B cells. This phenotype resembles that of transitional B cell subsets. Elevated percentages of these B cells were still found in 2 patients showing no decrease in EBV load after highly active antiretroviral therapy. Because transitional-like B cells persist concomitantly with high EBV load after highly active antiretroviral therapy, we suggest that this population might be an alternative EBV reservoir in patients with chronic HIV infection who have strongly reduced numbers of memory B cells. The consequences of EBV infection of immature B cells are discussed with regard to B cell maturation and a higher prevalence of B cell lymphoma in HIV‐infected patients.

Cell Reservoirs of the Epstein-Barr Virus in Biopsy-proven Lymphocytic Interstitial Pneumonitis in HIV-1 Subtype E Infected Children

Lymphoid interstitial pneumonitis (LIP), a frequent pulmonary complication in human immune deficiency virus (HIV)-infected pediatric patients, is characterized histologically by marked infiltration of lymphoid cells. Several theories have been suggested that LIP may be caused by Epstein-Barr virus (EBV). To identify the reservoir of EBV and pathogenesis of lymphoid infiltrates in HIV subtype E infected pediatric LIP, we examined the distribution and expression of EBV in the inflammatory cell recruitment in surgical lung biopsy-proven LIP from 9 vertically HIV subtype E-infected pediatric patients. The dominant microscopic feature of LIP demonstrated widespread widening of alveolar septum by mononuclear inflammatory cell infiltrate mainly composed of mature lymphocytes and plasma cells surrounding airways and expanding to the lung interstitium. EBV-encoded RNA (EBER) in situ hybridization, performed from paraffin-embedded lung tissues, revealed positive intranuclear signals in all 9 LIP cases. Interestingly, combined immunohistochemical and in situ hybridization analyses in 6 out of 9 LIP cases revealed 30% to 50% of the Langerhans and related dendritic cells were infected with EBV, whereas <30% of the T and B cells were infected with EBV. These results suggested that a chronic antigenic stimulus of EBV played important roles in the pathogenesis of LIP in these patients. This supports the notion that Langerhans cells (LCs) are more readily infected with EBV, indicating that LCs are reservoirs for EBV in lungs of HIV subtype E-infected pediatric LIP. And possibly LCs may play an important role in the recruitment of inflammatory cell infiltrates, especially T cells into these tissues. In addition, HIV may provide a milieu or microenvironment for the evolution of LIP, which represent an immunologic response to EBV infection. Interactions between LCs and related dendritic cells together with T cells are important for effective HIV and EBV replications.

Epstein–Barr virus T‐cell immunity despite rituximab

Immunosuppression following solid organ transplantation results in impaired T-cell immunity and risk of Epstein-Barr virus (EBV)-positive post-transplant lymphoproliferative disorders (PTLD). The B-cell targeting antibody rituximab has efficacy in PTLD. As B cells are the principle reservoir for EBV, we investigated the effect of rituximab on the persistence of EBV-specific CD8(+) T-cell immunity. To avoid the confounding factor of concurrent immunosuppression to prevent transplant rejection, immunity was analysed in non-transplanted lymphoma patients (i.e. a non-PTLD setting). Cytomegalovirus-specific T-cell immunity was assessed as an internal control. Our data demonstrated that circulating B cells were not critical for maintaining EBV-specific T-cell immunity.

Lymphoproliferation in children after liver transplantation.

Lymphoproliferation in children after liver transplantation.

Characterization of epstein-barr virus-infected mantle cell lymphoma lines.

It has been reported that Epstein-Barr virus (EBV) resides in resting B cells in vivo. However, an ideal in vitro system for studying EBV latent infection in vivo has not yet been established. In this study, a mantle cell lymphoma line, SP53, was successfully infected with a recombinant EBV containing a neomycin-resistant gene. The EBV-carrying SP53 cells were obtained by selection using G418. They expressed EBER-1, EBNAs, and LMP1; this expression pattern of the EBV genes was similar to that in a lymphoblastoid cell line (LCL). However, proliferation assay showed that the EBV-carrying SP53 cells have a doubling time of 73 h, compared with 57 h of SP53 cells. Transplantation of 10(8) SP53 cells to nude mice formed tumors in 4 of 10 mice inoculated, but the EBV-carrying SP53 cells did not. Unexpectedly, EBV infection reduced the proliferation and tumorigenicity of SP53 cells. However, the EBV-carrying SP53 cells showed higher resistance to apoptosis induced by serum starvation than did the SP53 cells. The inhibition of proliferation and the resistance to apoptosis induced in SP53 cells by EBV infection indicate that this cell line might to some extent provide a model of in vivo EBV reservoir cells.

Differential methylation of Epstein-Barr virus latency promoters facilitates viral persistence in healthy seropositive individuals.

Epstein-Barr virus (EBV) establishes a life-long infection in humans, with distinct viral latency programs predominating during acute and chronic phases of infection. Only a subset of the EBV latency-associated antigens present during the acute phase of EBV infection are expressed in the latently infected memory B cells that serve as the long-term EBV reservoir. Since the EBV immortalization program elicits a potent cellular immune response, downregulation of viral gene expression in the long-term latency reservoir is likely to facilitate evasion of the immune response and persistence of EBV in the immunocompetent host. Tissue culture and tumor models of restricted EBV latency have consistently demonstrated a critical role for methylation of the viral genome in maintaining the restricted pattern of latency-associated gene expression. Here we extend these observations to demonstrate that the EBV genomes in the memory B-cell reservoir are also heavily and discretely methylated. This analysis reveals that methylation of the viral genome is a normal aspect of EBV infection in healthy immunocompetent individuals and is not restricted to the development of EBV-associated tumors. In addition, the pattern of methylation very likely accounts for the observed inhibition of the EBV immortalization program and the establishment and maintenance of a restricted latency program. Thus, EBV appears to be the first example of a parasite that usurps the host cell-directed methylation system to regulate pathogen gene expression and thereby establish a chronic infection.

Hodgkin's disease of Waldeyer's ring. Clinical and histoimmunophenotypic findings and association with Epstein-Barr virus in 16 cases.

Waldeyer's ring is an uncommon, rarely reported primary site for Hodgkin's disease. We report a series of 16 such cases culled from the files of the Armed Forces Institute of Pathology and the National Cancer Institute. The patients' median age was 41 years (range, 14-74), and they presented with airway obstruction or unilateral tonsillar enlargement. The disease was localized to the Waldeyer's ring (stage I) in 46% of patients and extended to the cervical lymph nodes (stage II) in 39% and to the spleen (stage III) in 15%. Local radiation therapy, with or without chemotherapy, obtained a complete response in all but two patients. There was local recurrence in one patient and distant spread in three others. All patients for whom follow-up is available are alive without evidence of disease at 9 to 216 months (median, 20 months) except two who died of widespread Hodgkin's disease and two others who died of other causes. Histologically, eight cases were classified as mixed cellularity type (50%), four as nodular sclerosis (25%), and one as lymphocyte predominance, nodular (LPn; 6.3%); three others that showed interfollicular involvement were unclassified (18.7%). The Reed-Sternberg (RS) and atypical mononuclear cells in most cases of mixed cellularity and interfollicular types and all cases of nodular sclerosis had the classic immunophenotype (CD45-, CD20- and/or CD45RO-, CD15+ and/or CD30+). In the single case of LPn, they were of B-cell lineage (CD45+, CD20+, CD45RO-, CD15-, CD30-). In situ hybridization performed on routinely processed sections revealed Epstein-Barr virus (EBV) EBER1 mRNA in RS cells of eight of 12 cases studied (67%) only in mixed cellularity and nodular sclerosis, but not in LPn. We conclude that, however rarely, Hodgkin's disease of typical morphology and immunophenotype can originate in Waldeyer's ring. The incidence of EBV detection in the RS cells in our study is greater than that usually seen in nodal Hodgkin's disease in the United States. The greater prevalence of EBV-related Hodgkin's disease at this site is probably a reflection of the fact that the Waldeyer's ring is a reservoir for EBV.

Detection of Epstein-Barr virus DNA in anal scrapings from HIV-positive homosexual men.

Epstein-Barr virus (EBV) can infect epithelial cells as well as B lymphocytes. Infection of the male and female genital tracts has recently been demonstrated, and it has been suggested that the virus may be sexually transmissible. In our study we investigated whether EBV can be found in the anal region of sexually active homosexual men. Anal scrapings from HIV-positive homosexual men and a heterosexual control population were investigated using the polymerase chain reaction (PCR) to screen for EBV DNA. EBV DNA was detected in 8 of 27 anal samples (29.6%) from the homosexual men and 3 of 34 samples (8.8%) from the heterosexual men. Our study shows that, like the genital tract, the anal region can harbour EBV subclinically. This finding suggests that the anal region may be a reservoir for EBV and that sexual transmission of this virus may be possible.

Subclinical Epstein-Barr Virus Infection of both the Male and Female Genital Tract–Indication for Sexual Transmission

Epstein-Barr Virus (EBV) can infect B lymphocytes as well as epithelial cells of the oral cavity. Recently, infection of epithelial cells of the inflamed uterine cervix has been demonstrated, and EBV-DNA has been detected in urethral discharge of men suffering from genital infection. We investigated whether EBV can be found in the genital tract of both sexes independently from inflammatory disease states. Genital specimens of men and women of a sexually transmitted diseases outpatient clinic after excluding sexually transmitted diseases and clinically apparent signs of inflammation were investigated using the polymerase chain reaction to screen for EBV-DNA. In 13 of 47 samples (27.7%) swabbed from the uterine cervix, EBV-DNA could be detected. Similarly, 6 of 45 samples (13.3%) scraped from the sulcus coronarius contained EBV-DNA. Our study shows that the female genital tract and likewise the male genital tract can subclinically harbor EBV. These findings suggest i) that in addition to the oral cavity, the female and the male genital tract may be a reservoir for EBV and ii) that sexual transmission of this virus associated with an epidemiology different from that of oral infection may be possible.

Expression of proteins encoded by Epstein-Barr virus trans-activator genes depends on the differentiation of epithelial cells in oral hairy leukoplakia.

The Epstein-Barr virus (EBV) immediate early gene product BZLF1 was localized by indirect immunofluorescence to the cytoplasm of the basal epithelial layer at the lateral border and dorsum of tongue in human immunodeficiency virus-infected and -seronegative patients. Two biopsies of oral hairy leukoplakia revealed a sporadic cytoplasmic staining of the BHRF1 and BRLF1 gene products in the basal epithelial layer. The widespread presence of BZLF1 in the basal epithelial layer indicated that this cell layer contained EBV DNA and was probably directly infected by EBV. Nuclear localization of the immediate early and early gene products BZLF1, BHRF1, BRLF1, and BMLF1 was limited to oral hairy leukoplakia in human immunodeficiency virus-seropositive patients and revealed a codistribution with the virus capsid antigen. Our results indicate that the epithelium of the tongue is a potential reservoir for EBV and that in heavily immunocompromised patients EBV may move from the cytoplasm to the nucleus with increasing differentiation and be coactivated there during the terminal differentiation of epithelial cells at the lateral border and dorsum of tongue.

Spontaneous Lymphoblastoid Transformation of Cells Obtained from Human Tonsils

Spontaneous lymphoblastoid transformation of cells obtained from 25 human tonsils were investigated. Three Epstein-Barr virus (EBV) genome-positive lymphoblastoid cell lines were spontaneously established in tissue cultures in vitro from human tonsils. In addition, the frequency of spontaneous lymphoblastoid transformation was increased by the treatment of tumor promoter, 12-0-tetradecanoylphorbol-13-acetate and 18 lymphoblastoid cell lines were established. The data suggest that the human tonsil is a reservoir for EBV.