Nef binds p6* in GagPol during replication of human immunodeficiency virus type 1. 2004

Luciana J Costa, and Yong-Hui Zheng, and Jerica Sabotic, and Johnson Mak, and Oliver T Fackler, and B Matija Peterlin
Department of Medicine, University of California-San Francisco, UCSF-Mt. Zion Cancer Center, 2340 Sutter Street, San Francisco, CA 94115, USA.

The atypical Nef protein (NefF12) from human immunodeficiency virus type 1 strain F12 (HIV-1(F12)) interferes with virion production and infectivity via a mysterious mechanism. The correlation of these effects with the unusual perinuclear subcellular localization of NefF12 suggested that the wild-type Nef protein could bind to assembly intermediates in late stages of viral replication. To test this hypothesis, Nef from HIV-1(NL4-3) was fused to an endoplasmic reticulum (ER) retention signal (NefKKXX). This mutant NefKKXX protein recapitulated fully the effects of NefF12 on on Gag processing and virion production, either alone or as a CD8 fusion protein. Importantly, the mutant NefKKXX protein also localized to the intermediate compartment, between the ER and the trans-Golgi network. Furthermore, Nef bound the GagPol polyprotein in vitro and in vivo. This binding mapped to the C-terminal flexible loop in Nef and the transframe p6* protein in GagPol. The significance of this interaction was demonstrated by a genetic assay in which the release of a mutant HIV-1 provirus lacking the PTAP motif in the late domain that no longer binds Tsg101 was rescued by a Nef.Tsg101 chimera. Importantly, this rescue as well as incorporation of Nef into HIV-1 virions correlated with the ability of Nef to interact with GagPol. Our data demonstrate that the retention of Nef in the intermediate compartment interferes with viral replication and suggest a new role for Nef in the production of HIV-1.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D004721 Endoplasmic Reticulum A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed) Ergastoplasm,Reticulum, Endoplasmic
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D014771 Virion The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. Virus Particle,Viral Particle,Viral Particles,Particle, Viral,Particle, Virus,Particles, Viral,Particles, Virus,Virions,Virus Particles
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015685 Fusion Proteins, gag-pol Polyprotein products of a fused portion of retroviral mRNA containing the gag and pol genes. The polyprotein is synthesized only five percent of the time since pol is out of frame with gag, and is generated by ribosomal frameshifting. gag-pol Fusion Proteins,gag-pol Protein,gag-pol Fused Protein,Fused Protein, gag-pol,Fusion Proteins, gag pol,Protein, gag-pol,Protein, gag-pol Fused,Proteins, gag-pol Fusion,gag pol Fused Protein,gag pol Fusion Proteins,gag pol Protein
D015693 Gene Products, nef Products of the retroviral NEF GENE. They play a role as accessory proteins that influence the rate of viral infectivity and the destruction of the host immune system. nef gene products were originally found as factors that trans-suppress viral replication and function as negative regulators of transcription. nef stands for negative factor. nef Gene Products,nef Protein,3'-orf Protein,Gene Product, nef,3' orf Protein,nef Gene Product
D054311 nef Gene Products, Human Immunodeficiency Virus Proteins encoded by the NEF GENES of the HUMAN IMMUNODEFICIENCY VIRUS. nef Protein, Human Immunodeficiency Virus,HIV-3'-orf Protein,nef Protein, HIV,HIV 3' orf Protein,HIV nef Protein

Related Publications

Luciana J Costa, and Yong-Hui Zheng, and Jerica Sabotic, and Johnson Mak, and Oliver T Fackler, and B Matija Peterlin
May 1996, [Hokkaido igaku zasshi] The Hokkaido journal of medical science,
Luciana J Costa, and Yong-Hui Zheng, and Jerica Sabotic, and Johnson Mak, and Oliver T Fackler, and B Matija Peterlin
May 1993, Virology,
Luciana J Costa, and Yong-Hui Zheng, and Jerica Sabotic, and Johnson Mak, and Oliver T Fackler, and B Matija Peterlin
January 2002, Microbiology and immunology,
Luciana J Costa, and Yong-Hui Zheng, and Jerica Sabotic, and Johnson Mak, and Oliver T Fackler, and B Matija Peterlin
February 2007, Biological chemistry,
Luciana J Costa, and Yong-Hui Zheng, and Jerica Sabotic, and Johnson Mak, and Oliver T Fackler, and B Matija Peterlin
June 1994, Journal of virology,
Luciana J Costa, and Yong-Hui Zheng, and Jerica Sabotic, and Johnson Mak, and Oliver T Fackler, and B Matija Peterlin
April 2001, Journal of virology,
Luciana J Costa, and Yong-Hui Zheng, and Jerica Sabotic, and Johnson Mak, and Oliver T Fackler, and B Matija Peterlin
June 2004, The Journal of general virology,
Luciana J Costa, and Yong-Hui Zheng, and Jerica Sabotic, and Johnson Mak, and Oliver T Fackler, and B Matija Peterlin
August 2002, Journal of virology,
Luciana J Costa, and Yong-Hui Zheng, and Jerica Sabotic, and Johnson Mak, and Oliver T Fackler, and B Matija Peterlin
January 2005, Journal of virology,
Luciana J Costa, and Yong-Hui Zheng, and Jerica Sabotic, and Johnson Mak, and Oliver T Fackler, and B Matija Peterlin
May 2002, Journal of virology,
Copied contents to your clipboard!