Requirements for measles virus induction of RANTES chemokine in human astrocytoma-derived U373 cells

Interferons and chemokines play a critical role in regulating the host resp onse to viral infection. Measles virus, a member of the Paramyxoviridae fam ily, induces RANTES expression by astrocytes. We have examined the mechanis m 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 expres sion. Formalin-inactivated virus, which can bind but not fuse, and extensiv ely UV-irradiated virus, which can bind and fuse, were both ineffective. Th erefore, virus binding tol the cellular receptor CD46 and subsequent membra ne fusion were necessary, but not sufficient, to induce RANTES. UV irradiat ion of virus for less than 10 min proportionally inhibited viral transcript ion and RANTES expression. RANTES induction was decreased in infected cells treated with ribavirin, which inhibits measles virus transcription. Howeve r, RANTES mRNA was superinduced by measles virus in the presence of cyclohe ximide. These data suggest that partial transcription of the viral genome i s sufficient and necessary for RANTES induction, whereas viral protein synt hesis and replication are not required. This hypothesis was supported by th e fact that RANTES was induced through transient expression of the measles virus nucleocapsid gene but not by measles genes encoding P or L proteins o r 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.