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Journal of Virology, July 2001, p. 6292-6302, Vol. 75, No. 14
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.14.6292-6302.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Products of US22 Genes M140 and M141 Confer
Efficient Replication of Murine Cytomegalovirus in Macrophages
and Spleen
Laura K.
Hanson,
Jacquelyn S.
Slater,
Zaruhi
Karabekian,
Gina
Ciocco-Schmitt, and
Ann
E.
Campbell*
Department of Microbiology and Molecular Cell
Biology, Eastern Virginia Medical School, Norfolk, Virginia 23507
Received 25 January 2001/Accepted 16 April 2001
Efficient replication of murine cytomegalovirus (MCMV) in
macrophages is a prerequisite for optimal growth and spread of the virus in its natural host. Simultaneous deletion of US22 gene family
members M139, M140, and M141 results in impaired replication of MCMV in
macrophages and mice. In this study, we characterized the proteins
derived from these three genes and examined the impact of individual
gene deletions on viral pathogenesis. The M139, M140, and M141 gene
products were identified as early proteins that localize to both the
nucleus and cytoplasm in infected cells. Gene M139 encodes two
proteins, of 72 and 61 kDa, while M140 and M141 each encode a single
protein of 56 (pM140) and 52 (pM141) kDa, respectively. No role for the
M139 proteins in MCMV replication in macrophages or mice was determined
in these studies. In contrast, deletion of either M140 or M141 resulted
in impaired MCMV replication in macrophages and spleen tissue.
Replication of the M140 deletion mutant was significantly more impaired
than that of the virus lacking M141. Further analyses revealed that the
absence of the pM140 adversely affected pM141 levels by rendering the
latter protein unstable. Since the replication defect due to deletion of M140 was more profound than could be explained by the reduced half-life of pM141, pM140 must exert an additional, independent function in mediating efficient replication of MCMV in macrophages and
spleen tissue. These data indicate that the US22 genes M140 and M141
function both cooperatively and independently to regulate MCMV
replication in a cell type-specific manner and, thus, to influence
viral pathogenesis.
*
Corresponding author. Mailing address: Department of
Microbiology and Molecular Cell Biology, Eastern Virginia Medical
School, P.O. Box 1980, 700 W. Olney Rd., Norfolk, VA 23507. Phone:
(757) 446-5667. Fax: (757) 624-2255. E-mail:
campbeae{at}evms.edu.
Journal of Virology, July 2001, p. 6292-6302, Vol. 75, No. 14
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.14.6292-6302.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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