title: Infection of primary neurons mediated by nipah virus envelope proteins: role of host target cells in antiviral action.
abstract: We have previously described heterotypic peptides from parainfluenza virus that potently inhibit Nipah virus in vitro but are not efficacious in vivo. In contrast, our second-generation inhibitors, featuring a cholesterol moiety, are also efficacious in vivo. The difference between in vitro and in vivo results led us to investigate the basis for this discrepancy. Here, we compare the activities of the compounds in standard laboratory cells and in cells relevant to the natural tropism of Nipah virus, i.e., primary neurons, and show that while our first-generation inhibitors are poorly active in primary neurons, the cholesterol-conjugated compounds are highly potent. These results highlight the advantage of evaluating antiviral potency in cells relevant to natural host target tissue.
authors.affiliation: Department of Pediatrics and Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Talekar
authors.forename: Antonello
authors.initials: A
authors.lastname: Pessi
authors.forename: Matteo
authors.initials: M
authors.lastname: Porotto
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D004847:Epithelial Cells / Q000821:virology; D006801:Humans; D009474:Neurons / Q000821:virology*; D045405:Nipah Virus / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D010455:Peptides; D014759:Viral Envelope Proteins; D002784:Cholesterol