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Journal of Virology, March 1999, p. 1894-1901, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Cell Cycle Arrest during Measles Virus Infection: a
G0-Like Block Leads to Suppression of Retinoblastoma
Protein Expression
Denise
Naniche,1,*
Steven I.
Reed,2 and
Michael B. A.
Oldstone1
Division of Virology, Department of
Neuropharmacology,1 and
Department of
Molecular Biology,2 The Scripps Research
Institute, La Jolla, California 92037
Received 27 July 1998/Accepted 16 November 1998
One of the major mechanisms by which measles virus (MV) infection
causes disease and death is suppression of the immune response. The
nonresponsiveness of MV-infected human lymphocytes to mitogens and a
partial block in the G0/G1 phase of the cell
cycle observed in vitro is thought to reflect in vivo
immunosuppression. In order to molecularly dissect MV-induced
immunosuppression, we analyzed expression of surface activation markers
and cell cycle-regulatory proteins in MV-infected human T lymphocytes.
MV Edmonston (MV-Ed) could induce and maintain a high level of the
early activation marker CD69 in the absence of proliferation.
Expression of cyclins D3 and E, which positively control entry into S
phase, was also significantly decreased. Analysis of inhibitors of
progression into S phase showed that a high level of p27 was maintained
in the G0/G1-blocked subpopulation of
MV-Ed-infected cells compared to the proliferating MV-infected cells.
Furthermore, cell cycle-related upregulation of retinoblastoma (Rb)
protein synthesis did not occur in the MV-Ed-infected lymphocytes.
Acridine orange staining, which distinguishes cells in G0
from cells in G1, showed that RNA levels were not
upregulated following activation, which is consistent with cells
remaining in a G0 state. Although expression of surface
activation markers indicated entry into the cycle, intracellular Rb and
RNA levels suggested a quiescent state. These results indicate that MV
can uncouple activation of T lymphocytes from transition of
G0 to G1.
*
Corresponding author. Mailing address: The Scripps
Research Institute, 10550 N. Torrey Pines Rd., IMM6, La Jolla, CA
92037. Phone: (619) 784-8738. Fax: (619) 784-9981. E-mail:
naniche{at}scripps.edu.
Journal of Virology, March 1999, p. 1894-1901, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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