title: Interactions involved in pH protection of the alphavirus fusion protein.
abstract: The alphavirus membrane protein E1 mediates low pH-triggered fusion of the viral and endosome membranes during virus entry. During virus biogenesis E1 associates as a heterodimer with the transmembrane protein p62. Late in the secretory pathway, cellular furin cleaves p62 to the mature E2 protein and a peripheral protein E3. E3 remains bound to E2 at low pH, stabilizing the heterodimer and thus protecting E1 from the acidic pH of the secretory pathway. Release of E3 at neutral pH then primes the virus for fusion during entry. Here we used site-directed mutagenesis and revertant analysis to define residues important for the interactions at the E3-E2 interface. Our data identified a key residue, E2 W235, which was required for E1 pH protection and alphavirus production. Our data also suggest additional residues on E3 and E2 that affect their interacting surfaces and thus influence the pH protection of E1 during alphavirus exit.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Whitney
authors.initials: W
authors.lastname: Fields
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: margaret.kielian@einstein.yu.edu.
authors.forename: Margaret
authors.initials: M
authors.lastname: Kielian
mesh_terms: D000524:Alphavirus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018354:Alphavirus Infections / Q000821:virology*; D000818:Animals; D002460:Cell Line; D006801:Humans; D006863:Hydrogen-Ion Concentration; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D014759:Viral Envelope Proteins
keywords: Alphavirus; Class II fusion protein; Fusion protein biogenesis; Membrane fusion; Virus entry