title: N-terminally myristoylated feline foamy virus Gag allows Env-independent budding of sub-viral particles.
abstract: Foamy viruses (FVs) are distinct retroviruses classified as Spumaretrovirinae in contrast to the other retroviruses, the Orthoretrovirinae. As a unique feature of FVs, Gag is not sufficient for sub-viral particle (SVP) release. In primate and feline FVs (PFV and FFV), particle budding completely depends on the cognate FV Env glycoproteins. It was recently shown that an artificially added N-terminal Gag myristoylation signal (myr-signal) overcomes this restriction in PFV inducing an Orthoretrovirus-like budding phenotype. Here we show that engineered, heterologous N-terminal myr-signals also induce budding of the distantly related FFV Gag. The budding efficiency depends on the myr-signal and its location relative to the N-terminus of Gag. When the first nine amino acid residues of FFV Gag were replaced by known myr-signals, the budding efficiency as determined by the detection of extracellular SVPs was low. In contrast, adding myr-signals to the intact N-terminus of FFV Gag resulted in a more efficient SVP release. Importantly, budding of myr-Gag proteins was sensitive towards inhibition of cellular N-myristoyltransferases. As expected, the addition or insertion of myr-signals that allowed Env-independent budding of FFV SVPs also retargeted Gag to plasma membrane-proximal sites and other intracellular membrane compartments. The data confirm that membrane-targeted FV Gag has the capacity of SVP formation.
authors.affiliation: Department of Genome Modifications and Carcinogenesis, Research Program Infection and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Im Neuenheimer Feld 242, 69120 Heidelberg, Germany. y.liu@dkfz.de
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yong-Boum
authors.initials: YB
authors.lastname: Kim
authors.forename: Martin
authors.initials: M
authors.lastname: Löchelt
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002460:Cell Line; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D015683:Gene Products, gag / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019814:Myristic Acid / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D016092:Spumavirus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019065:Virus Assembly; D057074:Virus Release
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag; D019814:Myristic Acid