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Volume 8 Supplement 2

Frontiers of Retrovirology 2011

The role of murine leukemia virus glycosated Gag protein in virus replication

Murine leukemia viruses (MuLVs) encode an alternate form of Gag protein in addition to the standard Gag precursor polyprotein, glycosylated Gag (glyco-gag or gPr80gag). gPr80gag contains additional amino-terminal peptides, and it is glycosylated. Until recently the function of gPr80gag was unclear, but we have recently shown that gPr80gag facilitates viral budding and release through lipid rafts. Glyco-gag mutant virus is less efficiently released from fibroblasts, mutant virus has lower cholesterol content (and higher buoyant density), and less Gag precursor polyprotein (Pr65gag) is associated with detergent-resistant membranes in infected cells. The mechanism by which gPr80gag facilitates virus release is under investigation. The N-terminal 88 amino acids of gPr80gag are sufficient to enhance virus release, indicating that the Gag sequences on this protein are not required. Cellular La protein is involved in gPr80gag function, since over-expression of La phenocopies gPr80gag in facilitating virus release, and knockdown of La abrogates gPr80gag-enhancement of virus release. MuLV glyco-gag can also facilitate release of HIV-1 particles from transfected cells, which suggests that these two viruses may share mechanisms for directing virus release through lipid rafts. gPr80gagalso counteracts the murine APOBEC3 restriction factor (mA3) since gPr80gagmutant virus shows a defect for establishment of infection in wild-type mice, but not in mA3 knockout animals.

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Correspondence to Hung Fan.

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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Lipid Raft
  • Lower Cholesterol
  • Murine Leukemia Virus
  • Mutant Virus
  • Knockout Animal