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J Virol, April 1998, p. 3205-3212, Vol. 72, No. 4
Department of Medicine, Brigham and Women's
Hospital, Harvard Medical School, Boston, Massachusetts 02115
Received 16 September 1997/Accepted 11 December 1997
Lymphocryptoviruses (LCVs) naturally infecting Old World nonhuman
primates are closely related to the human LCV, Epstein-Barr virus
(EBV), and share similar genome organization and sequences, biologic properties, epidemiology, and pathogenesis. LCVs can efficiently immortalize B lymphocytes from the autologous species, but
the ability of a given LCV to immortalize B cells from other Old World
primate species is variable. We found that LCV from rhesus monkeys did
not immortalize human B cells, and EBV did not immortalize rhesus
monkey B cells. In this study, baboon LCV could not immortalize human
peripheral blood B cells but could readily immortalize rhesus monkey B
cells. Thus, efficient LCV-induced B-cell immortalization across
distant Old World primate species appears to be restricted by a
species-specific block. To further characterize this species
restriction, we first cloned the rhesus monkey LCV major membrane
glycoprotein and discovered that the binding epitope for the EBV
receptor, CD21, was highly conserved. Stable infections of human B
cells with recombinant amplicons packaged in rhesus monkey or baboon
LCV envelopes were also consistent with a species-restricted block
occurring after virus binding and penetration. Transient infections of
human B cells with simian LCV resulted in latent LCV EBNA-2 gene
expression and activation of cell CD23 gene expression.
EBV-immortalized human B cells could be coinfected with baboon LCV, and
the simian virus persisted and replicated in human B
cells. Thus, several lines of evidence indicate that the species
restriction for efficient LCV-induced B-cell immortalization occurs
beyond virus binding and penetration. This has important implications
for the study of LCV infection in Old World primate models and for
human xenotransplantation where simian LCVs may be inadvertently
introduced into humans.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Infection of Human B Lymphocytes with
Lymphocryptoviruses Related to Epstein-Barr Virus
*
Corresponding author. Mailing address: Channing
Laboratory, 181 Longwood Ave., Boston MA 02115. Phone: (617) 525-4258. Fax: (617) 525-4257. E-mail:
fwang{at}rics.bwh.harvard.edu.
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