CONICET | Buscador de Institutos y Recursos Humanos

Martinez, M. G., Belouzard S., Cordo S., Whittaker G.R and Candurra N.A Cell tropism of viruses is regulated by interactions between viral and cellular factors during the replication cycle. The entry and dissemination of viruses in several families can be mediated by C-type lectins such as hDC-SIGN and hL-SIGN. DC-SIGN is expressed in dendritic cells (DCs) and has been identified as a receptor for different enveloped viruses. In this report we studied JUNV ability to be internalized by hDC- or hL-SIGN. Immunofluorescence assays showed that infection of Vero cells was enhanced by the over expression of hDC-SIGN or hL-sign, whereas infection of non-permissive murine cell line, 3T3, can be rescued by the expression of hDC-or hL-SIGN. Treatment with mannan reduced infection, in immunofluorescence and PFU assays, of this lectin expressing cell lines, whereas anti-hDC/hL-SIGN antibodies blocked infection as seen by PFU assay. Therefore these lectins can act as a novel attachment factors that mediate entry of JUNV. We demonstrate that the human C type lectins hL-SIGN and hDC-SIGN enhances transduction by JUNV pseudovirus particles carrying only JUNV glycoprotein in cells devoid of the JUNV receptor, hTfR1, indicating that C-type lectins can mediate virus entry in the absence of the virus cellular receptor. In addition we started the endocytic pathway used by JUNV in cells expressing these lectins. Preliminary data show that the entry used in these cells would differ from the clathrin mediated endocytosis used in Vero cells. Altogether, this study characterizes early steps in the replication cycle of the arenavirus JUNV and provides additional information of new world arenavirus possible receptors.

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