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Journal of Virology, April 1999, p. 3117-3124, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Requirements for Measles Virus Induction of RANTES Chemokine in Human Astrocytoma-Derived U373 Cells

Katherine H. Noe,1 Cristina Cenciarelli,1,dagger Sue A. Moyer,2 Paul A. Rota,3 and Moon L. Shin1,*

Department of Pathology, School of Medicine, University of Maryland, Baltimore, Maryland 212011; Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida 326102; and Centers for Disease Control and Prevention, Atlanta, Georgia 303333

Received 2 October 1998/Accepted 4 January 1999

Interferons and chemokines play a critical role in regulating the host response to viral infection. Measles virus, a member of the Paramyxoviridae family, induces RANTES expression by astrocytes. We have examined the mechanism of this induction in U373 cells derived from a human astrocytoma. RANTES was induced in a dose- and time-dependent manner by measles virus infection. Inhibition of receptor binding by the anti-CD46 antibody TRA-2.10 and of virus-membrane fusion by the tripeptide X-Phe-Phe-Gly reduced RANTES expression. Formalin-inactivated virus, which can bind but not fuse, and extensively UV-irradiated virus, which can bind and fuse, were both ineffective. Therefore, virus binding to the cellular receptor CD46 and subsequent membrane fusion were necessary, but not sufficient, to induce RANTES. UV irradiation of virus for less than 10 min proportionally inhibited viral transcription and RANTES expression. RANTES induction was decreased in infected cells treated with ribavirin, which inhibits measles virus transcription. However, RANTES mRNA was superinduced by measles virus in the presence of cycloheximide. These data suggest that partial transcription of the viral genome is sufficient and necessary for RANTES induction, whereas viral protein synthesis and replication are not required. This hypothesis was supported by the fact that RANTES was induced through transient expression of the measles virus nucleocapsid gene but not by measles genes encoding P or L proteins or by leader RNA in A549 cells. Thus, transcription of specific portions of measles virus RNA, such as the nucleocapsid gene, appears able to generate the specific signaling required to induce RANTES gene expression.

* Corresponding author. Mailing address: Department of Pathology, School of Medicine, University of Maryland, 10 S. Pine St., Baltimore, MD 21201. Phone: (410) 706-7892. Fax: (410) 706-7706. E-mail: mshin{at}umaryland.edu.

dagger Present address: Dept. of Cardiology/Membrane Physiology, Rockefeller University, New York, NY 10021.

Journal of Virology, April 1999, p. 3117-3124, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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