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Lassa virus (LASV) is responsible for the deaths of thousands of people in West Africa annually. Genetic diversity among LASV strains is the highest among the Arenaviridae and represents a great challenge for vaccine development. Guinea pigs vaccinated with a ML29 reassortant vaccine experienced sterilizing immunity and complete protection when challenged on day 30 either with homologous virus or with the distantly related Nigerian isolate. Simultaneous vaccination-challenge or challenge on day 2 after vaccination also protected 60-100% of the animals against both strains, but without sterilizing immunity. These results indicate that simultaneous replication of ML29 and LASV attenuates the virulence of LASV infection.

Bradykinin (BK) and phorbol 12-myristate-13-acetate (PMA) were used in the present work to study the biosynthesis of proteoglycans (PG) during the cell cycle of endothelial cells. PMA, an activator of PKC, stimulated the synthesis of heparan sulfate proteoglycan (HSPG) secreted to the medium of endothelial cells mainly during the G(1) phase of the cell cycle [J. Cell. Biochem. 70 (1998) 563]. BK is a vasoactive peptide that increases calcium levels inside the cells indirectly stimulating PKC. Treatment of the endothelial cells with BK, as well as PMA, stimulated the synthesis of HSPG secreted to the medium and produced an antimitogenic effect on the cell cycle. These results led to the conclusion that PKC is directly involved in the synthesis of HSPG secreted to the medium. Also, comparing the effect showed by BK with PMA, one may suggest that different PKC isoforms are involved in these two processes and that their isoforms are mainly Ca(2+) dependent.