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Journal of Virology, March 1999, p. 2115-2125, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
CD21-Dependent Infection of an Epithelial Cell
Line, 293, by Epstein-Barr Virus
Joyce D.
Fingeroth,1
Margaret E.
Diamond,2
David R.
Sage,1
Jody
Hayman,2 and
John L.
Yates2,*
Divisions of Infectious Disease and
Experimental Medicine, Beth Israel Deaconess Medical Center and Harvard
Medical School, Boston, Massachusetts 02215,1
and
Department of Genetics, Roswell Park Cancer Institute,
Buffalo, New York 142632
Received 10 September 1998/Accepted 13 November 1998
Epstein-Barr virus (EBV) is invariably present in undifferentiated
nasopharyngeal carcinomas, is found sporadically in other carcinomas,
and replicates in the differentiated layer of the tongue epithelium in
lesions of oral hairy leukoplakia. However, it is not clear how
frequently or by what mechanism EBV infects epithelial cells normally.
Here, we report that a human epithelial cell line, 293, can be stably
infected by EBV that has been genetically marked with a selectable
gene. We show that 293 cells express a relatively low level of CD21,
that binding of fluorescein-labeled EBV to 293 cells can be detected,
and that both the binding of virus to cells and infection can be
blocked with antibodies specific for CD21. Two proteins known to form
complexes with CD21 on the surface of lymphoid cells, CD35 and CD19,
could not be detected at the surface of 293 cells. All infected clones
of 293 cells exhibited tight latency with a pattern of gene expression
similar to that of type II latency, but productive EBV replication and release of infectious virus could be induced inefficiently by forced
expression of the lytic transactivators, R and Z. Low levels of mRNA
specific for the transforming membrane protein of EBV, LMP-1, as well
as for LMP-2, were detected; however, LMP-1 protein was either
undetectable or near the limit of detection at less than 5% of the
level typical of EBV-transformed B cells. A slight increase in
expression of the receptor for epidermal growth factor, which can be
induced in epithelial cells by LMP-1, was detected at the cell surface
with two EBV-infected 293 cell clones. These results show that low
levels of surface CD21 can support infection of an epithelial cell line
by EBV. The results also raise the possibility that in a normal
infection of epithelial cells by EBV, the LMP-1 protein is not
expressed at levels that are high enough to be oncogenic and that there
might be differences in the cells of EBV-associated epithelial cancers
that have arisen to allow for elevated expression of LMP-1.
*
Corresponding author. Mailing address: Department of
Genetics, Roswell Park Cancer Institute, Elm and Carlton St., Buffalo, NY 14263. Phone: (716) 845-8964. Fax: (716) 845-8449. E-mail: yates{at}sc3101.med.buffalo.edu.
Journal of Virology, March 1999, p. 2115-2125, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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