Human immunodeficiency virus type 1 nucleocapsid p1 confers ESCRT pathway dependence.
To facilitate the release of infectious progeny virions, human immunodeficiency virus type 1 (HIV-1) exploits the Endosomal Sorting Complex Required for Transport (ESCRT) pathway by engaging Tsg101 and ALIX through late assembly (L) domains in the C-terminal p6 domain of Gag. However, the L domains in p6 are known to be dispensable for efficient particle production by certain HIV-1 Gag constructs that have the nucleocapsid (NC) domain replaced by a foreign dimerization domain to substitute for the assembly function of NC. We now show that one such L domain-independent HIV-1 Gag construct (termed Z(WT)) that has NC-p1-p6 replaced by a leucine zipper domain is resistant to dominant-negative inhibitors of the ESCRT pathway that block HIV-1 particle production. However, Z(WT) became dependent on the presence of an L domain when NC-p1-p6 was restored to its C terminus. Furthermore, when the NC domain was replaced by a leucine zipper, the p1-p6 region, but not p6 alone, conferred sensitivity to inhibition of the ESCRT pathway. In an authentic HIV-1 Gag context, the effect of an inhibitor of the ESCRT pathway on particle production could be alleviated by deleting a portion of the NC domain together with p1. Together, these results indicate that the ESCRT pathway dependence of HIV-1 budding is determined, at least in part, by the NC-p1 region of Gag.
Popova
Elena
E
Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Popov
Sergei
S
Göttlinger
Heinrich G
HG
D002460:Cell Line; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D046529:Microscopy, Electron, Transmission; D019251:Nucleocapsid / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D011995:Recombination, Genetic; D017384:Sequence Deletion; D057074:Virus Release; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
D056827:Endosomal Sorting Complexes Required for Transport; D054301:gag Gene Products, Human Immunodeficiency Virus