title: HIV Pol inhibits HIV budding and mediates the severe budding defect of Gag-Pol.
abstract: The prevailing hypothesis of HIV budding posits that the viral Gag protein drives budding, and that the Gag p6 peptide plays an essential role by recruiting host-cell budding factors to sites of HIV assembly. HIV also expresses a second Gag protein, p160 Gag-Pol, which lacks p6 and fails to bud from cells, consistent with the prevailing hypothesis of HIV budding. However, we show here that the severe budding defect of Gag-Pol is not caused by the absence of p6, but rather, by the presence of Pol. Specifically, we show that (i) the budding defect of Gag-Pol is unaffected by loss of HIV protease activity and is therefore an intrinsic property of the Gag-Pol polyprotein, (ii) the N-terminal 433 amino acids of Gag and Gag-Pol are sufficient to drive virus budding even though they lack p6, (iii) the severe budding defect of Gag-Pol is caused by a dominant, cis-acting inhibitor of budding in the HIV Pol domain, and (iv) Gag-Pol inhibits Gag and virus budding in trans, even at normal levels of Gag and Gag-Pol expression. These and other data support an alternative hypothesis of HIV budding as a process that is mediated by the normal, non-viral pathway of exosome/microvesicle biogenesis.
authors.affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Xin
authors.initials: X
authors.lastname: Gan
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gould
mesh_terms: D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D055354:Exosomes / Q000821:virology; D015685:Fusion Proteins, gag-pol / Q000378:metabolism*; D057809:HEK293 Cells; D006678:HIV / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D057074:Virus Release
chemical_list: D004279:DNA, Viral; D015685:Fusion Proteins, gag-pol