Η Αιτιοπαθολογική Σχέση του Ιού Epstein-Barr και της Τριχωτής Λευκοπλακίας
Τριάντος Α. Δημήτρης*
Εργαστήριο Στοματολογίας, Οδοντιατρική Σχολή Πανεπιστημίου Αθηνών (Διευθυντής: Καθ. Στ.Ι. Παπανικολάου)
* Διδάκτωρ Στοματολογίας Παν. του Λονδίνου, Μετα-διδακτορικός
Υπότροφος ΙΚΥ, Συνεργάτης Εργαστηρίου Στοματολογίας
Αρχεία Ελληνικής Στοματικής και Γναθοπροσωπικής Χειρουργικής 2(4): 250 - 258, 2001
ΠΕΡΙΛΗΨΗ
Η τριχωτή λευκοπλακία (ΤΛ) είναι μια από τις νοσολογικές οντότητες που έφερε στο φως η λοίμωξη
ΗΝ, αλλά έχει περιγραφεί (αν και πιο σπάνια) και σε άλλους ανοσοκατασταλμένους ασθενείς. Χαρακτηριστικά,
εμφανίζεται ως καλά προσφυόμενες λευκές/γκριζόλευκες πτυχωτές πλάκες στα πλάγια χείλη της
γλώσσας, αμφοτερόπλευρα. Η σπουδαιότητα της βλάβης είναι μεγάλη, καθώς και η μοναδική βιολογική
οντότητα, στην οποία ο ιός Epstein-Barr (EBV) αναπαράγεται πλούσια in vivo.
Η ΤΛ αντιπροσωπεύει λυτική μόλυνση με τον EBV σε απουσία λανθάνοντος φάσης. Η ακάνθωση και η
υπερπλασία, που παρατηρούνται στην ΤΛ είναι άμεσο αποτέλεσμα της συνδυασμένης ενέργειας των EBV-
κωδικοποιούμενων πρωτεϊνών. Η πρωτείνη BHRF1, ομόλογη με το αντι-αποπτωτικό ογκογονίδιο Bcl-2,
σε ιστούς ΤΛ, καθυστερεί την τελική διαφοροποίηση, δημιουργώντας ένα σταθερό κυτταρικό περιβάλλον
για την επιβίωση του ιού.
Εκτεταμένες μελέτες σε μοριακό επίπεδο έχουν καταδείξει την ποικιλότητα των στελεχών του EBV σε
ιστούς ΤΛ, αποτέλεσμα κυρίως, ομόλογων και ετερόλογων ανασυνδυασμών. Σε έδαφος ανοσοκαταστο-
λής, ο πολλαπλασιασμός, η αιματογενής διασπορά και η συνεχής επαναμόλυνση των γλωσσικών επιθηλιακών
κυττάρων από τα νέα αυτά στελέχη με το ιδιαίτερο παθογενετικό δυναμικό, πιθανόν να είναι υπεύθυνοι
για την τελική ανάπτυξη της τριχωτής λευκοπλακίας
Λέξεις κλειδιά: Τριχωτή λευκοπλακία, Ιός Epstein-Barr, HIV, Ανοσοκαταστολή, Γενετική ποικιλότητα του EBV
REFERENCES
Becker J, Leser U, Marschall M, Langford A, Jilg W, Gelderblor
H, Reichart P, Wolf H: Expression of proteins encoded b
Epstein-Barr virus trans-activator genes depends on th
differentiation of epithelial cells in oral hairy leukoplakie
Proc Natl Acad Sci USA 88: 8332-6, 1991
Blomgren J, Back H: Oral hairy leukoplakia in a patient wit
multiple myeloma. Oral Surg. Oral Med Oral Pathol Ore
Radiol Endod 82: 408-10, 1996
Boulter AW, Soltanpoor N, Swan AV, Birnbaum W, Johnso
NW, Teo CG: Risk factors associated with Epstein-Barr virus
replication in oral epithelial cells of HIV-infected individual
AIDS 10: 935-40, 1996
Brandwein M, Nuovo G, Ramer M, Orlowski W, Miller L
Epstein-Barr reactivation in hairy leukoplakia. Mod Pathol 9
298-303, 1996
Chen HL, Lung ML, Chan KH, Griffin BE, Ng NH: Tissu
distribution of Epstein-Barr virus genotypes. J Virol 7C
7301-5, 1996
Chrysomali E, Greenspan JS, Dekker N, Greenspan D, Rege.
JA: Apoptosis-associated proteins in oral hairy leukoplakia
Oral Dis 2: 279-84, 1996
Crawford DH, Weller I, Iliescu V, Wara DW: Epstein-Barr (EE
virus infection in homosexual men in London. Br J Vene
Dis 60: 258-64, 1984
Daniels TE, Greenspan D, Greenspan JS, Lennette E, Schiodt A
Petersen V, de Souza Y: Absence of Langerhans cells in on
hairy leukoplakia, an AIDS-associated lesion. J Invei
Dermatol 89: 178-82, 1987
Dawson CW, Eliopoulos AG, Dawson J, Young LS: BHRF1,
viral homologue of the Bcl-2 oncogene, disturbs epithelia
cell differentiation. Oncogene 10: 69-77, 1995
de Kaminsky AR, Kaminsky C, Fernandez Blanco G, Lago F
Sanchez G, Basso D, Fernandez Alonso G, Meiss R: Hair
leukoplakia in an HIV-seronegative patient. Int J Dermatc 34: 420-4, 1995
Eisenberg Ε, Krutchkoff D, Yamase H: Incidental oral hairy
leukoplakia in immunocompetent persons. A report of two
cases. Oral Surg Oral Med Oral Pathol 74: 332-3, 1992
Epstein JB, Sherlock CH, Wolber RA: Hairy leukoplakia after
bone marrow transplantation Oral Surg Oral Med Oral
Pathol 75: 690-5, 1993
Epstein JB, Fatahzadeh M, Matisic J, Anderson G: Exfoliative
cytology and electron microscopy in the diagnosis of hairy
leukoplakia. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 79: 564-9, 1995
Eversole LR, Jacobsen P, Stone CE, Freckleton V: Oral
condyloma planus (hairy leukoplakia) among homosexual
men: a clinicopathologic study of thirty-six cases. Oral Surg
Oral Med Oral Pathol 61: 249-55, 1986
Ficarra G, Gaglioti D, Di Pietro M, Adler-Storthz K: Oral hairy
leukoplakia: clinical aspects, histologic morphology and
differential diagnosis. Head Neck 13: 514-21, 1991a
Ficarra G, Miliani A, Adler-Storthz K, Woods-Francis K, Del
Mistro A, de Rossi A, Ricccardi R, Ravina A, De Maio E:
Recurrent oral condylomata acuminata and hairy
leukoplakia: an early sign of myelodysplastic syndrome in a
HIV-seronegative patient. J Oral Pathol Med 20: 398-402,
1991b
Fries KL, Sculley TB, Webster-Cyriaque J, Rajadurai P, Sadler
RH, Raab-Traub N: Identification of a novel protein encoded
by the BamHI A region of the Epstein-Barr virus. J Virol 71:
2765-71, 1997
Gilligan K, Rajadurai P, Rensick L, Raab-Traub N: Epstein-Barr
virus small nuclear RNAs are not expressed in permissively
infected cells in AIDS-associated leukoplakia. Proc Natl Acad
Sci USA 87: 8790-4, 1990
Gratama JW, Ernberg I: Molecular epidemiology of Epstein-Barr
virus infection. Adv Cancer Res 67: 197-225, 1995
Greenspan D, Greenspan JS, Conant M, Petersen K, Silverman
S, De Souza Y: Oral «hairy» leukoplakia in male
homosexuals: Evidence of association with both
papilomavirus and a herpes-group virus. Lancet 2: 831-4,
1984
Greenspan JS, Grenspan D, Lennette ET, Abrams DI, Conant
MA, Petersen V, Freese UK: Replication of Epstein-Barr Virus
within the epithelial cells of oral «hairy» leukoplakia, an
AIDS-associated lesion. Ν Engl J Med 313: 1564-71, 1985
Greenspan D, Greenspan JS, Hearst NG, Pan LZ, Conant MA,
Abrams DI, Hollander H, Levy JA: Relation of oral hairy
leukoplakia to infection with the human immunodeficiency
virus and the risk of developing AIDS. J Infect Dis 155: 475-
81, 1987
Greenspan JS, Greenspan D: Oral hairy leukoplakia: diagnosis
and management. Oral. Surg Oral Med Oral Pathol 67: 396-
403, 1989
Henle G, Henle W, Horwitz CA: Antibodies to Epstein-Barr virusassociated
nuclear antigen in infectious mononucleosis J
Infect Dis 130: 231-9, 1974
Horner D, Lewis M, Farrell PJ: Novel hypotheses for the roles of
EBNA-1 and BHRF1 in EBV-related cancers. Intervirology
38: 195-205, 1995
Jekins PJ, Farrell PJ: Are particular Epstein-Barr virus stains
linked to disease? Semin Cancer Biol 7: 209-15, 1996
Katz MH, Greenspan D, Heinic GS, Chan AK, Hollander H,
Chernoff D, Greenspan JS: Resolution of Hairy Leukoplakia:
An observational Trial of Zidovudine versus No Treatment. J
Infect Dis 164: 1240-1, 1991
King GN, Healy CM, Glover MT, Kwan JT, Williams DM, Leigh
IM, Thornhill MH: Prevalence and risk factors associated with
leukoplakia, hairy leukoplakia, erythematous candidiasis,
and gingival hyperplasia in renal transplant recipients. Oral
Surg Oral Med Oral Pathol 78: 718-26, 1994
Kolokotronis A, Kioses V, Antoniades D, Mandraveli K, Doutsos
I, Papanayotou P: Immunologic status in patients infected
with HIV with oral candidiasis and hairy leukoplakia. Oral
Surg Oral Med Oral Pathol 78: 41-6, 1994
Labandeira J, Peteiro C, Toribio J: Hairy leukoplakia and HIV-2.
A case report and review of the literature. Clin Exp Dermatol
19: 335-40, 1994
Lozada-Nur F, Robinson J, Regezi JA: Oral hairy leukoplakia in
non immunosuppressed patients. Report of four cases. Oral
Surg Oral Med Oral Pathol 78: 599-602,1994
Mabruk MJ, Flint SR, Toner M, Balluz I, Coleman D, Sallivan D,
Atkins GJ: In situ hybridization and the polymerase chain
reation (PCR) in the analysis of biopsies and exfoliative
cytology specimens for definitive diagnosis of oral hairy
leukoplakia (OHL). J Oral Pathol Med 23: 302-8, 1994
Miller G, Rabson M, Heston L: Epstein-Barr virus with
heterogeneous DNA disrupts latency. J Virol 50: 174-82,
1984
Nicolatou O, Nikolatos G, Fisfis M, Belegrati M, Papadaki T,
Oikonomaki E, Kaimantis T: Oral hairy leukoplakia in a
patients with acute lymphocytic leukemia. Oral Dis 5: 76-9,
1999
Niedobitec G, Young LS, Lau R, Brooks L, Greenspan D,
Greenspan JS, Rickinson AB: Epstein-Barr virus infection in
oral hairy leukoplakia: virus replication in the absence of a
detectable latent phase. J Gen Virol 72: 3035-46, 1991
Patton DF, Shirley P, Raab-Traub N, Resnick L, Sixbey JW:
Defective viral DNA in Epstein-Barr virus-associated oral
hairy leukoplakia. J Virol 64: 397-400, 1990
Patton LL, McKaig R, Strauss R, Rogers D, Eron J J Jr: Changing
prevalence of oral manifestations of human immunodeficiency
virus in the era of protease inhibitor therapy. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 89: 299-304,
2000
Penaranda ME, Lagenaur LA, Pierik LT, Berline JW, MacPhail
LA, Greenspan D, Greenspan JS, Palefsky JM: Expression of
Epstein-Barr virus BMRF-2 and BDLF-3 genes in hairy
leukoplakia. J Gen Virol 78: 3361-70, 1997
Raab-Traub Ν, Webster-Cyriaque J: Epstein-Barr virus infection
and expression in oral lesions. Oral Dis 3: S164-170, 1997
Reed KD, Fowler CB, Brannon RB: Ultrastructural detection of
herpes-type virions by negative staining in oral hairy
leukoplakia. Am J Clin Pathol 90: 305-8, 1988
Reggiani M, Pauluzzi P: Hairy Leukoplakia in Liver Transplant
Patient. Acta Dermatol Venereol 70: 87-8, 1990
Reichart PA, Langford A, Gelderblom HR, Pohle HD, Becker J,
Wolf H: Oral hairy leukoplakia: observations in 95 cases and
review of the literature. J Oral Pathol Med 18: 410-5, 1989
Rickinson AB, Kieff E: Epstein-Barr virus. In: Fields B, Knipe D,
Howley P, et al. eds. Virology, Third Edition. Lippincott-
Raven Publishers: Philadelphia, 1996, pp. 2397-446
Schiodt M, Greenspan D, Daniels TE, Greenspan JS: Clinical
and histologic spectrum of oral hairy leukoplakia. Oral Surg
Oral Med Oral Pathol 64: 716-20, 1987
Schiodt M, Bakilana PB, Hiza JF, Shao JF, Bygbjerg IB, Mbaga
I, Vestergaard BF, Nielsen CM, Lauritzen E, Lerche B: Oral
candidiasis and hairy leukoplakia correlate with HIV infection
in Tanzania. Oral Surg Oral Med Oral Pathol 69: 591-6,
1990
Schmidt-Westhausen A, Gelderblom HR, Reichart PA: Oral hairy
leukoplakia in an HIV-seronegative heart transplant patient.
J Oral Pathol Med 19: 192-4, 1990
Sugihara K, Reupke H, Schmidt-Westhausen A, Pohle HD,
Gelderblom HR, Reichan PA: Negative staining EM for the
detection of Epstein-Barr virus in oral hairy leukoplakia. J
Oral Pathol Med 19: 367-70, 1990
Syrjanen S, Laine P, Niemela M, Happonen RP: Oral hairy
leukoplakia is not a specific sign of HIV-infection but related
to immunosuppression in general. J Oral Pathol Med 18: 28-
31, 1989
Talacko AA, Teo CG, Griffin BE, Johnson NW: Epstein-Barr
virus receptors but not viral DNA are present in normal and
malignant oral epithelium. J. Oral Pathol. Med. 20: 20-5,
1991
Tao Q, Srivastava G, Chan AC, Chung LP, Loke SL, Ho FC:
Evidence for lytic infection by Epstein-Barr virus in mucosal
lymphocytes instead of nasopharyngeal Epithelial cells in
normal individuals. J Med Virol 45: 71-7, 1995
Thomas JA, Felix DH, Wray D, Southam JC, Cubie HA
Crawford DH: Epstein-Barr virus gene expression an»
epithelial cell differentiation in oral hairy leukoplakia. Am
Pathol 139: 1369-80, 1991
Triantos D, Boulter AW, Leao JC, Di Alberti L, Porter SR, Scull
CM, Birnbaum W, Johnson NW, Teo CG: Diversity c
naturally occuring Epstein-Barr virus revealed by nucleotid
sequence polymorphism in hypervariable domains in th
BamHI Κ and Ν subgenomic regions. J Gen Virol 79: 2809
17, 1998a
Triantos D, Leao JC, Porter SR, Scully CM, Teo CG: Tissu
distribution of Epstein-Barr genotypes in hosts co-infected b
HIV. AIDS 12: 2141-6, 1998b
Walling DM, Edmiston SN, Sixbey JW, Abdel-Hamid M, Resnic
L, Raab-Traub N: Coinfection with multiple strains of th
Epstein-Barr virus in human immunodeficiency virus
associated hairy leukoplakia. Proc Natl Acad Sci USA 8S
6560-4, 1992
Webster Cyriaque J, Edwards RH, Quinlivan EB, Patton L, Wol
D, Raab-Traub N: Epstein-Barr virus and human herpesviru
8 prevalence in human immunodeficiency virus-associate
oral mucosal lesions. J Infect Dis 175, 1324-32, 1997
Wilson JB, Weinberg W, Johnson R, Yuspa Sr Levine Ac
Expression of the BNLF-1 oncogene of Epstein-Barr virus i
the skin of transgenic mice induces hyperplasia and aberrar
expression of keratin 6. Cell 61: 1315-27, 1990
Wolf H, Haus M, Wilmes E: Persistence of Epstein-Barr virus i
the parotid gland. J Virol 51: 795-8.
Young LS, Lau R, Rowe M, Niedobitek G, Packham C
Shanahan F, Rowe DT, Greenspan D, Greenspan Ji
Rickinson AB: Differentiation-associated expression of th
Epstein-Barr virus BZLF1 transactivator protein in oral hair
leukoplakia. J Virol 65: 2868-74, 1991
Εργαστήριο Στοματολογίας, Οδοντιατρική Σχολή Πανεπιστημίου Αθηνών (Διευθυντής: Καθ. Στ.Ι. Παπανικολάου)
* Διδάκτωρ Στοματολογίας Παν. του Λονδίνου, Μετα-διδακτορικός
Υπότροφος ΙΚΥ, Συνεργάτης Εργαστηρίου Στοματολογίας
Αρχεία Ελληνικής Στοματικής και Γναθοπροσωπικής Χειρουργικής 2(4): 250 - 258, 2001
ΠΕΡΙΛΗΨΗ
Η τριχωτή λευκοπλακία (ΤΛ) είναι μια από τις νοσολογικές οντότητες που έφερε στο φως η λοίμωξη
ΗΝ, αλλά έχει περιγραφεί (αν και πιο σπάνια) και σε άλλους ανοσοκατασταλμένους ασθενείς. Χαρακτηριστικά,
εμφανίζεται ως καλά προσφυόμενες λευκές/γκριζόλευκες πτυχωτές πλάκες στα πλάγια χείλη της
γλώσσας, αμφοτερόπλευρα. Η σπουδαιότητα της βλάβης είναι μεγάλη, καθώς και η μοναδική βιολογική
οντότητα, στην οποία ο ιός Epstein-Barr (EBV) αναπαράγεται πλούσια in vivo.
Η ΤΛ αντιπροσωπεύει λυτική μόλυνση με τον EBV σε απουσία λανθάνοντος φάσης. Η ακάνθωση και η
υπερπλασία, που παρατηρούνται στην ΤΛ είναι άμεσο αποτέλεσμα της συνδυασμένης ενέργειας των EBV-
κωδικοποιούμενων πρωτεϊνών. Η πρωτείνη BHRF1, ομόλογη με το αντι-αποπτωτικό ογκογονίδιο Bcl-2,
σε ιστούς ΤΛ, καθυστερεί την τελική διαφοροποίηση, δημιουργώντας ένα σταθερό κυτταρικό περιβάλλον
για την επιβίωση του ιού.
Εκτεταμένες μελέτες σε μοριακό επίπεδο έχουν καταδείξει την ποικιλότητα των στελεχών του EBV σε
ιστούς ΤΛ, αποτέλεσμα κυρίως, ομόλογων και ετερόλογων ανασυνδυασμών. Σε έδαφος ανοσοκαταστο-
λής, ο πολλαπλασιασμός, η αιματογενής διασπορά και η συνεχής επαναμόλυνση των γλωσσικών επιθηλιακών
κυττάρων από τα νέα αυτά στελέχη με το ιδιαίτερο παθογενετικό δυναμικό, πιθανόν να είναι υπεύθυνοι
για την τελική ανάπτυξη της τριχωτής λευκοπλακίας
Λέξεις κλειδιά: Τριχωτή λευκοπλακία, Ιός Epstein-Barr, HIV, Ανοσοκαταστολή, Γενετική ποικιλότητα του EBV
REFERENCES
Becker J, Leser U, Marschall M, Langford A, Jilg W, Gelderblor
H, Reichart P, Wolf H: Expression of proteins encoded b
Epstein-Barr virus trans-activator genes depends on th
differentiation of epithelial cells in oral hairy leukoplakie
Proc Natl Acad Sci USA 88: 8332-6, 1991
Blomgren J, Back H: Oral hairy leukoplakia in a patient wit
multiple myeloma. Oral Surg. Oral Med Oral Pathol Ore
Radiol Endod 82: 408-10, 1996
Boulter AW, Soltanpoor N, Swan AV, Birnbaum W, Johnso
NW, Teo CG: Risk factors associated with Epstein-Barr virus
replication in oral epithelial cells of HIV-infected individual
AIDS 10: 935-40, 1996
Brandwein M, Nuovo G, Ramer M, Orlowski W, Miller L
Epstein-Barr reactivation in hairy leukoplakia. Mod Pathol 9
298-303, 1996
Chen HL, Lung ML, Chan KH, Griffin BE, Ng NH: Tissu
distribution of Epstein-Barr virus genotypes. J Virol 7C
7301-5, 1996
Chrysomali E, Greenspan JS, Dekker N, Greenspan D, Rege.
JA: Apoptosis-associated proteins in oral hairy leukoplakia
Oral Dis 2: 279-84, 1996
Crawford DH, Weller I, Iliescu V, Wara DW: Epstein-Barr (EE
virus infection in homosexual men in London. Br J Vene
Dis 60: 258-64, 1984
Daniels TE, Greenspan D, Greenspan JS, Lennette E, Schiodt A
Petersen V, de Souza Y: Absence of Langerhans cells in on
hairy leukoplakia, an AIDS-associated lesion. J Invei
Dermatol 89: 178-82, 1987
Dawson CW, Eliopoulos AG, Dawson J, Young LS: BHRF1,
viral homologue of the Bcl-2 oncogene, disturbs epithelia
cell differentiation. Oncogene 10: 69-77, 1995
de Kaminsky AR, Kaminsky C, Fernandez Blanco G, Lago F
Sanchez G, Basso D, Fernandez Alonso G, Meiss R: Hair
leukoplakia in an HIV-seronegative patient. Int J Dermatc 34: 420-4, 1995
Eisenberg Ε, Krutchkoff D, Yamase H: Incidental oral hairy
leukoplakia in immunocompetent persons. A report of two
cases. Oral Surg Oral Med Oral Pathol 74: 332-3, 1992
Epstein JB, Sherlock CH, Wolber RA: Hairy leukoplakia after
bone marrow transplantation Oral Surg Oral Med Oral
Pathol 75: 690-5, 1993
Epstein JB, Fatahzadeh M, Matisic J, Anderson G: Exfoliative
cytology and electron microscopy in the diagnosis of hairy
leukoplakia. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 79: 564-9, 1995
Eversole LR, Jacobsen P, Stone CE, Freckleton V: Oral
condyloma planus (hairy leukoplakia) among homosexual
men: a clinicopathologic study of thirty-six cases. Oral Surg
Oral Med Oral Pathol 61: 249-55, 1986
Ficarra G, Gaglioti D, Di Pietro M, Adler-Storthz K: Oral hairy
leukoplakia: clinical aspects, histologic morphology and
differential diagnosis. Head Neck 13: 514-21, 1991a
Ficarra G, Miliani A, Adler-Storthz K, Woods-Francis K, Del
Mistro A, de Rossi A, Ricccardi R, Ravina A, De Maio E:
Recurrent oral condylomata acuminata and hairy
leukoplakia: an early sign of myelodysplastic syndrome in a
HIV-seronegative patient. J Oral Pathol Med 20: 398-402,
1991b
Fries KL, Sculley TB, Webster-Cyriaque J, Rajadurai P, Sadler
RH, Raab-Traub N: Identification of a novel protein encoded
by the BamHI A region of the Epstein-Barr virus. J Virol 71:
2765-71, 1997
Gilligan K, Rajadurai P, Rensick L, Raab-Traub N: Epstein-Barr
virus small nuclear RNAs are not expressed in permissively
infected cells in AIDS-associated leukoplakia. Proc Natl Acad
Sci USA 87: 8790-4, 1990
Gratama JW, Ernberg I: Molecular epidemiology of Epstein-Barr
virus infection. Adv Cancer Res 67: 197-225, 1995
Greenspan D, Greenspan JS, Conant M, Petersen K, Silverman
S, De Souza Y: Oral «hairy» leukoplakia in male
homosexuals: Evidence of association with both
papilomavirus and a herpes-group virus. Lancet 2: 831-4,
1984
Greenspan JS, Grenspan D, Lennette ET, Abrams DI, Conant
MA, Petersen V, Freese UK: Replication of Epstein-Barr Virus
within the epithelial cells of oral «hairy» leukoplakia, an
AIDS-associated lesion. Ν Engl J Med 313: 1564-71, 1985
Greenspan D, Greenspan JS, Hearst NG, Pan LZ, Conant MA,
Abrams DI, Hollander H, Levy JA: Relation of oral hairy
leukoplakia to infection with the human immunodeficiency
virus and the risk of developing AIDS. J Infect Dis 155: 475-
81, 1987
Greenspan JS, Greenspan D: Oral hairy leukoplakia: diagnosis
and management. Oral. Surg Oral Med Oral Pathol 67: 396-
403, 1989
Henle G, Henle W, Horwitz CA: Antibodies to Epstein-Barr virusassociated
nuclear antigen in infectious mononucleosis J
Infect Dis 130: 231-9, 1974
Horner D, Lewis M, Farrell PJ: Novel hypotheses for the roles of
EBNA-1 and BHRF1 in EBV-related cancers. Intervirology
38: 195-205, 1995
Jekins PJ, Farrell PJ: Are particular Epstein-Barr virus stains
linked to disease? Semin Cancer Biol 7: 209-15, 1996
Katz MH, Greenspan D, Heinic GS, Chan AK, Hollander H,
Chernoff D, Greenspan JS: Resolution of Hairy Leukoplakia:
An observational Trial of Zidovudine versus No Treatment. J
Infect Dis 164: 1240-1, 1991
King GN, Healy CM, Glover MT, Kwan JT, Williams DM, Leigh
IM, Thornhill MH: Prevalence and risk factors associated with
leukoplakia, hairy leukoplakia, erythematous candidiasis,
and gingival hyperplasia in renal transplant recipients. Oral
Surg Oral Med Oral Pathol 78: 718-26, 1994
Kolokotronis A, Kioses V, Antoniades D, Mandraveli K, Doutsos
I, Papanayotou P: Immunologic status in patients infected
with HIV with oral candidiasis and hairy leukoplakia. Oral
Surg Oral Med Oral Pathol 78: 41-6, 1994
Labandeira J, Peteiro C, Toribio J: Hairy leukoplakia and HIV-2.
A case report and review of the literature. Clin Exp Dermatol
19: 335-40, 1994
Lozada-Nur F, Robinson J, Regezi JA: Oral hairy leukoplakia in
non immunosuppressed patients. Report of four cases. Oral
Surg Oral Med Oral Pathol 78: 599-602,1994
Mabruk MJ, Flint SR, Toner M, Balluz I, Coleman D, Sallivan D,
Atkins GJ: In situ hybridization and the polymerase chain
reation (PCR) in the analysis of biopsies and exfoliative
cytology specimens for definitive diagnosis of oral hairy
leukoplakia (OHL). J Oral Pathol Med 23: 302-8, 1994
Miller G, Rabson M, Heston L: Epstein-Barr virus with
heterogeneous DNA disrupts latency. J Virol 50: 174-82,
1984
Nicolatou O, Nikolatos G, Fisfis M, Belegrati M, Papadaki T,
Oikonomaki E, Kaimantis T: Oral hairy leukoplakia in a
patients with acute lymphocytic leukemia. Oral Dis 5: 76-9,
1999
Niedobitec G, Young LS, Lau R, Brooks L, Greenspan D,
Greenspan JS, Rickinson AB: Epstein-Barr virus infection in
oral hairy leukoplakia: virus replication in the absence of a
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