title: Mutations in the amino terminus of foamy virus Gag disrupt morphology and infectivity but do not target assembly.
abstract: Foamy viruses (FVs) assemble using pathways distinct from those of orthoretroviruses. FV capsid assembly takes place near the host microtubule-organizing center (MTOC). Assembled capsids then migrate by an unknown mechanism to the trans-Golgi network to colocalize with the FV glycoprotein, Env. Interaction with Env is required for FV capsid egress from cells; the amino terminus of FV Gag contains a cytoplasmic targeting/retention signal that is responsible for targeting assembly to the MTOC. A mutant Gag was constructed by addition of a myristylation (M) signal in an attempt to target assembly to the plasma membrane and potentially overcome the dependence upon Env for budding (S. W. Eastman and M. L. Linial, J. Virol. 75:6857-6864, 2001). Using this and additional mutants, we now show that assembly is not redirected to the plasma membrane. Addition of an M signal leads to gross morphological defects. The aberrant particles still assemble near the MTOC but do not produce infectious virus. Although extracellular Gag can be detected in a pelletable form in the absence of Env, the mutant particles contain very little genomic RNA and are less dense. Our analyses indicate that the amino terminus of Gag contains an Env interaction domain that is critical for bona fide egress of assembled capsids.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109-1024, USA.
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Life
authors.forename: Eun-Gyung
authors.initials: EG
authors.lastname: Lee
authors.forename: Scott W
authors.initials: SW
authors.lastname: Eastman
authors.forename: Maxine L
authors.initials: ML
authors.lastname: Linial
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D015686:Gene Products, env / Q000378:metabolism*; D015683:Gene Products, gag / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D016092:Spumavirus / Q000235:genetics* / Q000648:ultrastructure; D019065:Virus Assembly / Q000235:genetics*
chemical_list: D017931:DNA Primers; D015686:Gene Products, env; D015683:Gene Products, gag