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The nucleocapsid region of HIV-1 Gag cooperates with the PTAP and LYPXnL late domains to recruit the cellular machinery necessary for viral budding.

Publication ,  Journal Article
Dussupt, V; Javid, MP; Abou-Jaoudé, G; Jadwin, JA; de La Cruz, J; Nagashima, K; Bouamr, F
Published in: PLoS Pathog
March 2009

HIV-1 release is mediated through two motifs in the p6 region of Gag, PTAP and LYPX(n)L, which recruit cellular proteins Tsg101 and Alix, respectively. The Nucleocapsid region of Gag (NC), which binds the Bro1 domain of Alix, also plays an important role in HIV-1 release, but the underlying mechanism remains unclear. Here we show that the first 202 residues of the Bro1 domain (Bro(i)) are sufficient to bind Gag. Bro(i) interferes with HIV-1 release in an NC-dependent manner and arrests viral budding at the plasma membrane. Similar interrupted budding structures are seen following over-expression of a fragment containing Bro1 with the adjacent V domain (Bro1-V). Although only Bro1-V contains binding determinants for CHMP4, both Bro(i) and Bro1-V inhibited release via both the PTAP/Tsg101 and the LYPX(n)L/Alix pathways, suggesting that they interfere with a key step in HIV-1 release. Remarkably, we found that over-expression of Bro1 rescued the release of HIV-1 lacking both L domains. This rescue required the N-terminal region of the NC domain in Gag and the CHMP4 binding site in Bro1. Interestingly, release defects due to mutations in NC that prevented Bro1 mediated rescue of virus egress were rescued by providing a link to the ESCRT machinery via Nedd4.2s over-expression. Our data support a model in which NC cooperates with PTAP in the recruitment of cellular proteins necessary for its L domain activity and binds the Bro1-CHMP4 complex required for LYPX(n)L-mediated budding.

Duke Scholars

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

March 2009

Volume

5

Issue

3

Start / End Page

e1000339

Location

United States

Related Subject Headings

  • gag Gene Products, Human Immunodeficiency Virus
  • Virology
  • Viral Proteins
  • Transfection
  • Transcription Factors
  • Polymerase Chain Reaction
  • Nucleocapsid
  • Mutagenesis, Site-Directed
  • Immunoprecipitation
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dussupt, V., Javid, M. P., Abou-Jaoudé, G., Jadwin, J. A., de La Cruz, J., Nagashima, K., & Bouamr, F. (2009). The nucleocapsid region of HIV-1 Gag cooperates with the PTAP and LYPXnL late domains to recruit the cellular machinery necessary for viral budding. PLoS Pathog, 5(3), e1000339. https://doi.org/10.1371/journal.ppat.1000339
Dussupt, Vincent, Melodi P. Javid, Georges Abou-Jaoudé, Joshua A. Jadwin, Jason de La Cruz, Kunio Nagashima, and Fadila Bouamr. “The nucleocapsid region of HIV-1 Gag cooperates with the PTAP and LYPXnL late domains to recruit the cellular machinery necessary for viral budding.PLoS Pathog 5, no. 3 (March 2009): e1000339. https://doi.org/10.1371/journal.ppat.1000339.
Dussupt V, Javid MP, Abou-Jaoudé G, Jadwin JA, de La Cruz J, Nagashima K, et al. The nucleocapsid region of HIV-1 Gag cooperates with the PTAP and LYPXnL late domains to recruit the cellular machinery necessary for viral budding. PLoS Pathog. 2009 Mar;5(3):e1000339.
Dussupt, Vincent, et al. “The nucleocapsid region of HIV-1 Gag cooperates with the PTAP and LYPXnL late domains to recruit the cellular machinery necessary for viral budding.PLoS Pathog, vol. 5, no. 3, Mar. 2009, p. e1000339. Pubmed, doi:10.1371/journal.ppat.1000339.
Dussupt V, Javid MP, Abou-Jaoudé G, Jadwin JA, de La Cruz J, Nagashima K, Bouamr F. The nucleocapsid region of HIV-1 Gag cooperates with the PTAP and LYPXnL late domains to recruit the cellular machinery necessary for viral budding. PLoS Pathog. 2009 Mar;5(3):e1000339.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

March 2009

Volume

5

Issue

3

Start / End Page

e1000339

Location

United States

Related Subject Headings

  • gag Gene Products, Human Immunodeficiency Virus
  • Virology
  • Viral Proteins
  • Transfection
  • Transcription Factors
  • Polymerase Chain Reaction
  • Nucleocapsid
  • Mutagenesis, Site-Directed
  • Immunoprecipitation
  • Humans