title: Equine infectious anemia virus utilizes host vesicular protein sorting machinery during particle release.
abstract: A final step in retrovirus assembly, particle release from the cell, is modulated by a small motif in the Gag protein known as a late domain. Recently, human immunodeficiency virus type 1 (HIV-1) and Moloney murine leukemia virus (M-MuLV) were shown to require components of the cellular vacuolar protein sorting (VPS) machinery for efficient viral release. HIV-1 interacts with the VPS pathway via an association of HIV-1 Gag with TSG101, a component of the cellular complexes involved in VPS. Equine infectious anemia virus (EIAV) is unique among enveloped viruses studied to date because it utilizes a novel motif, YPDL in Gag, as a late domain. Our analysis of EIAV assembly demonstrates that EIAV Gag release is blocked by inhibition of the VPS pathway. However, in contrast to HIV-1, EIAV Gag release is insensitive to TSG101 depletion and EIAV particles do not contain significant levels of TSG101. Finally, we demonstrate that fusing EIAV Gag directly with another cellular component of the VPS machinery, VPS28, can restore efficient release of an EIAV Gag late-domain mutant. These results provide evidence that retroviruses can interact with the cellular VPS machinery in several different ways to accomplish particle release.
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076, USA.
authors.forename: Giancarlo O
authors.initials: GO
authors.lastname: Tanzi
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Piefer
authors.forename: Paul
authors.initials: P
authors.lastname: Bates
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D004860:Infectious Anemia Virus, Equine / Q000502:physiology*; D008856:Microscopy, Fluorescence; D009154:Mutation; D021381:Protein Transport / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins; D014771:Virion / Q000378:metabolism*; D000099177:Tsg101 Protein
chemical_list: D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D020690:GTPase-Activating Proteins; D015683:Gene Products, gag; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D000099177:Tsg101 Protein; C476409:VPS28 protein, human