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N-Terminally Myristoylated Feline Foamy Virus Gag Allows Env-Independent Budding of Sub-Viral Particles
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
Current address: Institute for Molecular Biosciences, Center for Biomolecular Magnetic Resonance, Johann Wolfgang Goethe-University Frankfurt, Max von Laue-Straße 9, 60438 Frankfurt am Main, Germany.
* Author to whom correspondence should be addressed.
Received: 29 August 2011; in revised form: 4 November 2011 / Accepted: 4 November 2011 / Published: 14 November 2011
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.
Keywords: feline foamy virus; retrovirus; assembly; budding; release; sub-viral particles; myristoylation
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Liu, Y.; Kim, Y.-B.; Löchelt, M. N-Terminally Myristoylated Feline Foamy Virus Gag Allows Env-Independent Budding of Sub-Viral Particles. Viruses 2011, 3, 2223-2237.
Liu Y, Kim Y-B, Löchelt M. N-Terminally Myristoylated Feline Foamy Virus Gag Allows Env-Independent Budding of Sub-Viral Particles. Viruses. 2011; 3(11):2223-2237.
Liu, Yang; Kim, Yong-Boum; Löchelt, Martin. 2011. "N-Terminally Myristoylated Feline Foamy Virus Gag Allows Env-Independent Budding of Sub-Viral Particles." Viruses 3, no. 11: 2223-2237.