| Virus Name | Lassa virus |
| Virus Short Name | LASV |
| Order | Unassigned |
| Virus Family | Arenaviridae |
| Virus Subfamily | N.A. |
| Genus | Mammarenavirus |
| Species | Lassa virus |
| Host | Rodents and human |
| Cell Tropism | N.A. |
| Associated Disease | Hemorrhagic fever |
| Mode of Transmission | Zoonosis , fomite |
| VIPR DB link | https://www.viprbrc.org/brc/vipr_allSpecies_search.spg?method=SubmitForm&decorator=arena |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/negative-sense-rna-viruses-2011/w/negrna_viruses/203/arenaviridae |
| Virus Host DB link | N.A. |
| Paper Title | Lassa Virus cell entry via dystroglycan involves an unusual pathway of macropinocytosis |
| Author's Name | Joel Oppliger, Giulia Torriani, Antonio Herrador, Stefan Kunz |
| Journal Name | Journal Of Virology |
| Pubmed ID | 27147735 |
| Abstract | The pathogenic Old World arenavirus Lassa virus (LASV) causes a severe hemorrhagic fever with a high rate of mortality in humans. Several LASV receptors, including dystroglycan (DG), TAM receptor tyrosine kinases, and C-type lectins, have been identified, suggesting complex receptor use. Upon receptor binding, LASV enters the host cell via an unknown clathrin- and dynamin-independent pathway that delivers the virus to late endosomes, where fusion occurs. Here we investigated the mechanisms underlying LASV endocytosis in human cells in the context of productive arenavirus infection, using recombinant lymphocytic choriomeningitis virus (rLCMV) expressing the LASV glycoprotein (rLCMV-LASVGP). We found that rLCMV-LASVGP entered human epithelial cells via DG using a macropinocytosis-related pathway independently of alternative receptors. Dystroglycan-mediated entry of rLCMV-LASVGP required sodium hydrogen exchangers, actin, and the GTPase Cdc42 and its downstream targets, p21-activating kinase-1 (PAK1) and Wiskott-Aldrich syndrome protein (N-Wasp). Unlike other viruses that enter cells via macropinocytosis, rLCMV-LASVGP entry did not induce overt changes in cellular morphology and hardly affected actin dynamics or fluid uptake. Screening of kinase inhibitors identified protein kinase C, phosphoinositide 3-kinase, and the receptor tyrosine kinase human hepatocyte growth factor receptor (HGFR) to be regulators of rLCMV-LASVGP entry. The HGFR inhibitor EMD 1214063, a candidate anticancer drug, showed antiviral activity against rLCMV-LASVGP at the level of entry. When combined with ribavirin, which is currently used to treat human arenavirus infection, EMD 1214063 showed additive antiviral effects. In sum, our study reveals that DG can link LASV to an unusual pathway of macropinocytosis that causes only minimal perturbation of the host cell and identifies cellular kinases to be possible novel targets for therapeutic intervention. |
| Used Model | A549 and Caco-2 |
| DOI | 10.1128/JVI.00257-16 |
