Persistence and Transition of Epstein‐Barr Virus Genotypes in the Pathogenesis of Oral Hairy Leukoplakia

Walling, Dennis M.; Etienne, Wiguins; Ray, Autumn J.; Flaitz, Catherine M.; Nichols, C. Mark

doi:10.1086/421708

Cited by 34 publications

(30 citation statements)

References 46 publications

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“…These data confirm the suspected presence of a cellular reservoir of latent EBV infection in the oral epithelium that serves as a reactivation source for productive EBV replication (44,47,50). Although multiple previous studies have failed to identify EBV in the lower layers of oral epithelium (21,24,25,28,32,40,48,(50)(51)(52), the singular success of this study is likely a result of two important methodological advantages.…”

Section: Cd11csupporting

confidence: 74%

“…Subjects were either healthy individuals or patients infected with human immunodeficiency virus (HIV), with or without AIDS. Tissue specimens obtained included 100 ml of venous blood, tongue and buccal mucosal epithelium cells collected by nonsurgical oral epithelial brush biopsy (45), and tongue and buccal mucosal tissue collected by surgical excisional biopsy (44,(46)(47)(48)50). Some subjects contributed specimens more than once, and the numerical identity of each subject was maintained throughout the study.…”

Section: Methodsmentioning

confidence: 99%

“…Model 3 proposes that EBV virions produced by B lymphocytes in oral lymphoid tissues (26) gain access to and infect middle-and upper-layer oral epithelial cells as a result of microscopic traumatic epithelial injury, such as that which occurs during mastication. However, this model is contradicted by evidence that EBV transitions into oral epithelium as cell-associated latent infection and that EBV reactivates from a persistent latent oral mucosal source to productively replicate in the oral epithelium (44,47,50).…”

Section: Epstein-barr Virus (Ebv) Is a Human Herpesvirus That Ultimatmentioning

confidence: 99%

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Epstein-Barr Virus Infection of Langerhans Cell Precursors as a Mechanism of Oral Epithelial Entry, Persistence, and Reactivation

Walling

Ray²,

Nichols

et al. 2007

J Virol

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Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with many malignant and nonmalignant human diseases. Life-long latent EBV persistence occurs in blood-borne B lymphocytes, while EBV intermittently productively replicates in mucosal epithelia. Although several models have previously been proposed, the mechanism of EBV transition between these two reservoirs of infection has not been determined. 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. Epstein-Barr virus (EBV) is a human herpesvirus that ultimately infects 95% of adults worldwide. EBV is transmitted via mucosal fluids and establishes life-long persistent infection.Although persistent infection is asymptomatic in most people, EBV is associated with benign syndromes, including infectious mononucleosis and oral hairy leukoplakia, and a wide variety of both lymphoid and mucosal epithelial malignancies. Persistent latent EBV infection occurs in memory B lymphocytes that circulate in blood (22). While latent EBV infection also occurs in some epithelial malignancies (29), EBV infection of epithelial cells typically results in productive replication, as demonstrated in oral hairy leukoplakia (9) and in normal oral epithelium (8,10,48).Three different models have previously been proposed to explain the transition of EBV from the latent reservoir of infection in blood-borne B lymphocytes to sites of productive replication in oral epithelium. Model 1 proposes that B lymphocytes carrying latent EBV infection migrate from the blood to the epithelium, where the EBV reactivates and infects adjacent epithelial cells (12), but evidence of intraepithelial B lymphocytes in normal oral epithelium or in oral hairy leukoplakia is lacking (30, 33). Model 2 proposes that EBV virions produced by B lymphocytes in the oral submucosa bind submucosal EBV-specific dimeric immunoglobulin A (IgA) and enter basal oral epithelial cells by endocytosis via the polymeric Ig receptor (37), but the polymeric Ig receptor is not expressed in oral epithelium (23). Model 3 proposes that EBV virions produced by B lymphocytes in oral lymphoid tissues (26) gain access to and infect middle-and upper-layer oral epithelial cells as a result of microscopic traumatic epithelial injury, such as that which occurs during mastication. However, this model is contradicted by evidence that EBV transitions into oral epithelium as cell-associated latent infecti...

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Section: Cd11csupporting

confidence: 74%

Section: Methodsmentioning

confidence: 99%

Section: Epstein-barr Virus (Ebv) Is a Human Herpesvirus That Ultimatmentioning

confidence: 99%

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Epstein-Barr Virus Infection of Langerhans Cell Precursors as a Mechanism of Oral Epithelial Entry, Persistence, and Reactivation

Walling

Ray²,

Nichols

et al. 2007

J Virol

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“…EBV is the causative agent of infectious mononucleosis, and is associated with hairy leukoplakia (HL) and certain lymphoid and epithelial cancers such as Burkitt's lymphoma, immunoblastic lymphoma, Hodgkin's lymphoma, and nasopharyngeal cancer [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Detection of the Epstein–Barr Virus (EBV) by In situ Hybridization as Definitive Diagnosis of Hairy Leukoplakia

Braz‐Silva

Rezende

Ortega

et al. 2008

Head and Neck Pathol

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Histopathological findings in cases of hairy leukoplakia (HL) are not exclusive to this lesion. A total of 36 tissue samples from patients previously diagnosed with HL based solely on morphological aspects were used in this study. Our purpose was to confirm the presence of EpsteinBarr virus (EBV) in these tissue samples by in situ hybridization (ISH), and to compare the detection of EBV with specific histopathological findings observed in each case. Among the 36 specimens, 80.55% were EBV positive, confirming the previous clinical and histhophatological diagnosis. None of the histopathological findings analyzed correlated with the presence or absence of EBV. This shows that a definitive diagnosis of HL cannot be established based on histopathological findings alone. Because there are many important implications on the establishment of definitive diagnosis of HL, the detection of EBV by ISH is obligatory.

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“…Wirus przenoszony jest poprzez bliski kontakt z wydzielinami z jamy ustnej [6,9,10,12,14]. Zakaże-nia EBV wiążą się również z innymi schorzeniami, takimi jak mononukleoza zakaźna, rak jamy nosowo-gardłowej, chłonia-ki z limfocytów T i chłoniaki nieziarnicze, jednak jedynymi przejawami klinicznymi uznawanymi za związane z zakaże-niem replikatywnym wirusem EBV są OHL i mononukleoza zakaźna [15,16]. Rozpoznanie różnicowe OHL powinno uwzględniać leukoplakię jamy ustnej, liszaj płaski, kandydozę rzekomobłoniastą, przewlekłą kandydozę przerostową i język geograficzny [5].…”

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The value of the exfoliative cytology to the diagnosis of oral hairy leukoplakia - Case report

Kula¹,

Batista²,

Henn³

et al. 2015

Polski Przegląd Otorynolaryngologiczny

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ABSTRACT:Oral hairy leukoplakia is a lesion that generally occurs within the tongue. It is characterized by a white patch on the side of the tongue with a corrugated or hairy appearance. The OHL affects patients with HIV infection and has characteristics that differ from oral leukoplakia. The etiology of oral hairy leukoplakia is linked to the infection of epithelial cells by Epstein-Barr virus. The objective of this paper was to report a case of atypical oral hairy leukoplakia in a patient with HIV infection. A male patient, 43 years old, was hospitalized complaining of abdominal pain and symptoms suggestive of jaundice. A white plaque was identified on his tongue during a clinical examination. That lesion was painless and not removable by scraping. A liquid-based cytology was performed and cytological analysis revealed structures suggestive of Candida sp. and cytological changes consistent with oral hairy leukoplakia (Cowdry type A inclusion bodies, and ground-glass nuclei). Exfoliative cytology is a reliable test that can be used by a dentist and otolaryngologists to determine the diagnosis of atypical cases of oral hairy leukoplakia.

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Persistence and Transition of Epstein‐Barr Virus Genotypes in the Pathogenesis of Oral Hairy Leukoplakia

Cited by 34 publications

References 46 publications

Epstein-Barr Virus Infection of Langerhans Cell Precursors as a Mechanism of Oral Epithelial Entry, Persistence, and Reactivation

Epstein-Barr Virus Infection of Langerhans Cell Precursors as a Mechanism of Oral Epithelial Entry, Persistence, and Reactivation

Detection of the Epstein–Barr Virus (EBV) by In situ Hybridization as Definitive Diagnosis of Hairy Leukoplakia

The value of the exfoliative cytology to the diagnosis of oral hairy leukoplakia - Case report

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