title: Viral entry inhibitors block dengue antibody-dependent enhancement in vitro.
abstract: Severe dengue virus (DENV) disease symptoms, including dengue hemorrhagic fever and dengue shock syndrome, have been correlated with the presence of pre-existing antibodies that enhance rather than neutralize infections in Fc receptor bearing cells. These antibodies can originate from previous infection with a different serotype of dengue, or from waning antibody titers that occur in infants and young children as they are weaned from breast milk that contains protective dengue-specific antibodies. Despite the apparent importance of this antibody dependent enhancement (ADE) effect, there has been no description of any specific inhibitors of this process. We explored DENV entry inhibitors as a potential strategy to block ADE. Two different peptide entry inhibitors were tested for the ability to block antibody-mediated DENV-2 infection of human, FcRII bearing K562 cells in vitro. Both peptides were able to inhibit ADE, showing that entry inhibitors are possible candidates for the development of specific treatment for severe DENV infection.
authors.affiliation: Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, FL 33965, USA. cnicholson@fgcu.edu
authors.forename: Cindo O
authors.initials: CO
authors.lastname: Nicholson
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Costin
authors.forename: Dawne K
authors.initials: DK
authors.lastname: Rowe
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Ekachai
authors.initials: E
authors.lastname: Jenwitheesuk
authors.forename: Ram
authors.initials: R
authors.lastname: Samudrala
authors.forename: Sharon
authors.initials: S
authors.lastname: Isern
authors.forename: Scott F
authors.initials: SF
authors.lastname: Michael
mesh_terms: D019067:Antibody-Dependent Enhancement; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D010455:Peptides / Q000494:pharmacology; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D010455:Peptides