Alpha- and flaviviruses contain class II fusion
proteins, which form ion-permeable pores in the target membrane during virus entry. The pores generated during entry of the alphavirus Semliki Forest virus have been shown previously to be blocked by
lanthanide ions. Here, analyses of the influence of rare earth
ions on the entry of the flaviviruses West Nile virus and Uganda S virus revealed an unexpected effect of
lanthanide ions. The results showed that a 30 s treatment of cells with an appropriate
lanthanide ion changed the cellular chemistry into a state in which the cells no longer supported the multiplication of flaviviruses. This change occurred in cells treated before, during or after
infection, did not inhibit multiplication of Semliki Forest virus and did not interfere with host-cell multiplication. The change was generated in vertebrate and insect cells, and was elicited in the presence of
actinomycin D. In vertebrate cells, the change was elicited specifically by La(3+), Ce(3+), Pr(3+) and Nd(3+). In insect cells, additional
lanthanide ions had this activity. Further analyses showed that
lanthanide ion treatment blocked the ability of the host cell to support the replication of flavivirus
RNA. These results open two areas of research: the study of molecular alterations induced by
lanthanide ion treatment in uninfected cells and the analysis of the resulting modifications of the flavivirus
RNA replicase complex. The findings possibly open the way for the development of a general
chemotherapy against flavivirus diseases such as
Dengue fever,
Japanese encephalitis,
West Nile fever and
yellow fever.