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Journal of Virology, August 2000, p. 7610-7618, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Hairy Leukoplakia: an Unusual Combination of
Transforming and Permissive Epstein-Barr Virus Infections
J.
Webster-Cyriaque,1,2
J.
Middeldorp,3 and
N.
Raab-Traub1,4,*
Lineberger Comprehensive Cancer
Center,1 Department of
Microbiology,4 and UNC School of
Dentistry, Department of Dental Ecology,2
University of North Carolina, Chapel Hill, North Carolina, and
Organon Teknika, Boxtel, The
Netherlands3
Received 12 October 1999/Accepted 9 May 2000
Human herpesviruses are characterized by distinct states of
infection. Typically in permissive herpesvirus infection, abundant virus production results in cell lysis. In latent transforming Epstein-Barr virus (EBV) infection, viral proteins that induce cell
growth are expressed. The immunodeficiency-associated hairy leukoplakia
(HLP) lesion is the only pathologic manifestation of permissive EBV
infection; however, within HLP, viral proteins characteristic of latent
infection have also been detected. In this study, we further analyzed
expression of EBV latent genes and investigated their contribution to
the unique histologic phenotype of HLP. Coexpression of lytic and
transforming viral proteins was detected simultaneously within
individual HLP keratinocytes. LMP1 has now been shown to be uniformly
expressed in the affected tissue, and it is associated and colocalizes
with tumor necrosis factor receptor-associated factor (TRAF) signaling
molecules. Effects induced by activated TRAF signaling that were
detected in HLP included activation of NF-
B and c-Jun terminal
kinase 1 (JNK1) and upregulated expression of epidermal growth factor receptor (EGFR), CD40, A20, and TRAFs. This study identifies a novel
state of EBV infection with concurrent expression of replicative and
transforming proteins. It is probable that both replicative and latent
proteins contribute to HLP development and induce many of the
histologic features of HLP, such as acanthosis and hyperproliferation. In contrast to other permissive herpesvirus infections, expression of
EBV transforming proteins within the permissively infected HLP tissue
enables epithelial cell survival and may enhance viral replication.
*
Corresponding author. Mailing address: Lineberger
Comprehensive Cancer Center, CB 7295, University of North Carolina,
Chapel Hill, NC 27599-7295. Phone: (919) 966-1701. Fax: (919) 966-3015. E-mail: nrt{at}med.unc.edu.
Journal of Virology, August 2000, p. 7610-7618, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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